Alzheimer's disease research
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages)(Learn how and when to remove this template message)
|Alzheimer's disease research|
There are different approaches in Alzheimer's disease research. One approach is to reduce amyloid beta, for example with bapineuzumab, an antibody in phase III studies for patients in mild to moderate stage; semagacestat, a γ-secretase inhibitor, MPC-7869; and UB-311, ACC-001 or CAD106, vaccines against amyloid beta. Other approaches are neuroprotective agents, like AL-108 (phase II completed); or metal-protein interaction attenuation, as is the case of PBT2 (phase II completed). Yet another approach is to use general cognitive enhancers, as may be the case for memantine, a pharmaceutical approved in the United States and European Union to treat symptoms of moderate-to-severe AD. In animals, ultrasound has been used for penetrating the blood-brain barrier and activating microglial cells to eliminate amyloid beta and restored memory function. Finally, there are basic investigations on the origin and mechanisms of Alzheimer's disease.
- 1 Treatments in clinical development
- 1.1 Immunotherapy to amyloid beta
- 1.2 Targeting the production of amyloid beta peptide
- 1.3 Metal-protein interaction attenuation
- 1.4 Statins
- 1.5 Metabolic correction
- 1.6 Other pharmaceuticals
- 1.6.1 Allopregnanolone
- 1.6.2 Angiotensin receptor blockers
- 1.6.3 Antibiotic therapy
- 1.6.4 Antiviral therapy
- 1.6.5 Cannabis
- 1.6.6 Dimebon
- 1.6.7 Etanercept
- 1.6.8 Insulin sensitizers and Intranasal insulin
- 1.6.9 Methylthioninium chloride
- 1.6.10 Sigma receptors
- 1.6.11 Translocator protein
- 1.6.12 TrkB agonists
- 2 Disease-modifying drug candidates
- 3 Non-imaging biomarkers
- 4 Ultrasound therapy
- 5 Bioinformatics approach
- 6 Pathogenesis and biomarkers
- 7 Pharmacology
- 8 References
- 9 External links
Treatments in clinical development
Several potential treatments for Alzheimer's disease are under investigation, including several compounds being studied in phase 3 clinical trials. The most important clinical research is focused on potentially treating the underlying disease pathology, for which reduction of amyloid beta is a common target of compounds under investigation.
Immunotherapy to amyloid beta
Immunotherapy or vaccination for Alzheimer's stimulates the immune system to attack beta-amyloid. One approach is active immunization, which would stimulate a permanent immune response. The vaccine AN-1792 showed promise in mouse and early human trials, but in a 2002 Phase II trial, 6% of subjects (18 of 300) developed serious brain inflammation resembling meningoencephalitis, and the trial was stopped. In long-term followups, 20% of subjects had developed high levels of antibodies to beta-amyloid. While placebo-patients and non-antibody responders worsened, these antibody-responders showed a degree of stability in cognitive levels as assessed by the neuropsychological test battery (although not by other measures), and had lower levels of the protein tau in their cerebrospinal fluid. These results may suggest reduced disease activity in the antibody-responder group. Autopsies found that immunization resulted in clearance of amyloid plaques, but did not prevent progressive neurodegeneration.
A Phase IIA study of ACC-001, a modified version of AN-1792, is now recruiting subjects.
Also derived from the AN-1792 immunotherapy program, there is an infused antibody approach termed a passive vaccine in that it does not invoke the immune system and would require regular infusions to maintain the artificial antibody levels. Micro-cerebral hemorrhages may be a threat to this process.
Bapineuzumab, an antibody to amyloid-β, was previously being developed; however, the drug failed in phase 3 clinical trials. The antibody was designed as essentially identical to the natural antibody triggered by the earlier AN-1792 vaccine.
A recent study showed FDA-approved cancer drugs, PD-1 inhibitors, may benefit patients with Alzheimer's disease. The study used a mouse model of Alzheimer's disease and an antibody against PD-1 to demonstrate a statistically significant reduction in amyloid-β plaques and improved cognitive performance.
Targeting the production of amyloid beta peptide
Gamma secretase inhibition
Gamma secretase is a protein complex thought to be a fundamental building block in the development of the amyloid beta peptide. A gamma secretase inhibitor, semagacestat, failed to show any benefit to Alzheimer's disease patients in clinical trials.
Gamma secretase modulation
Tarenflurbil (MPC-7869, formerly R-flubiprofen) is a gamma secretase modulator sometimes called a selective amyloid beta 42 lowering agent. It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide. Negative results were announced regarding tarenflurbil in July 2008 and further development was canceled.
Beta secretase inhibition
Metal-protein interaction attenuation
PBT2 is an 8-hydroxy quinoline that removes copper and zinc from cerebrospinal fluid, which are held to be necessary catalysts for amyloid beta aggregation. This drug has been in a Phase II trial for early Alzheimers and which has reported preliminarily promising, but not detailed, results.
Simvastatin, a statin, stimulates brain vascular endothelial cells to create a beta-amyloid ejector. The use of this statin may have a causal relationship to decreased development of the disease.
This approach is based on the prominent aspect of Alzheimer's disease, which is common for many other neurodegenerative diseases: energy deficit. It has first been noted for the case of insulin insufficiency in the brain of Alzheimer's patients. Because of that Alzheimer's disease has been called Type 3 diabetes and the insulin modification therapies are in pharmaceutical's pipelines.
Several other pharmaceuticals are under investigation to treat Alzheimer's disease.
Allopregnanolone has been identified as a potential drug agent. Levels of neurosteroids such as allopregnanolone decline in the brain in old age and AD. Allopregnanolone has been shown to aid the neurogenesis that reverses cognitive deficits in a mouse model of AD.
Angiotensin receptor blockers
A retrospective analysis of five million patient records with the US Department of Veterans Affairs system found that different types of commonly used anti-hypertensive medications had very different AD outcomes. Those patients taking angiotensin receptor blockers (ARBs) were 35—40% less likely to develop AD than those using other anti-hypertensives.
Several studies using antibiotics in animal models of Alzheimer's Disease indicated that minocycline and doxycycline exerted a protective effect in preventing neuron death and slowing the onset of the disease.
A preliminary trial of antibiotic therapy with doxycycline and rifampin at McMaster University had indicated that it was effective in delaying the progress of the disease: "In conclusion, a 3-month course of doxycycline and rifampin reduced cognitive worsening at 6 months of follow-up in patients with mild to moderate AD." A re-examination of the same data using "AUC analysis of the pooled index showed significant treatment effect over the 12-month period". However, when these preliminary findings were followed up with a subsequent larger trial, they found that "doxycycline or rifampin, alone or in combination, has no beneficial effects on cognition or function in [Alzheimer's disease]."
Also in July 2008 results were announced of a study in which an antihistamine that was formerly available in Russia, Dimebon, was given to a group of AD patients. The group receiving Dimebon improved somewhat over the 6 months of the study (and this continued for the next six months), whereas those on placebo deteriorated. Unfortunately the consecutive phase-III trial failed to show significant positive effects in the primary and secondary endpoints. The sponsors acknowledged in March 2010 that initial results of the phase III trial showed that while the drug had been well tolerated, its outcomes did not significantly differ from the placebo control.
As a TNF inhibitor, etanercept is currently being studied for its potential use to help treat dementia. Several studies suggest that increased levels of tumor necrosis factor (TNF) correlates to worsening psychiatric symptoms and neurodegeneration.
Insulin sensitizers and Intranasal insulin
Recent studies suggest an association between insulin resistance and AD (fat cell sensitivity to insulin can decline with aging): In clinical trials, a certain insulin sensitizer called "rosiglitazone" improved cognition in a subset of AD patients; in vitro, beneficial effects of Rosiglitazone on primary cortical rat neurons have been demonstrated. Initial research suggests intranasal insulin, increasing insulin levels in the brain with minimal insulin increase in the rest of the body, might also be utilized. Preclinical studies show that insulin clears soluble beta-amyloid from the brain within minutes after a systemic injection in diabetic transgenic mice modeling AD.
In July 2008, researchers announced positive results from methylthioninium chloride (MTC), (trade name: Rember) a drug that dissolved Tau polymers. Phase II results indicate that it is the first therapy that has success in modifying the course of disease in mild to moderate AD.
Originally considered an enigmatic protein, the sigma-1 receptor has been identified as a unique ligand-regulated molecular chaperone in the endoplasmic reticulum of cells. This discovery led to the review of many proposed roles of this receptor in many neurological diseases including Alzheimer's.
R7 is a prodrug of 7,8-dihydroxyflavone, an agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF). R7 is currently in preclinical development for the treatment of Alzheimer's disease.
Disease-modifying drug candidates
|Target/Approach||Notes (Theoretical)||Candidate Name||Trial Phase||Trial Start Date||Expected End Date||Planned Enrollment||AD population targeted (severity)||AD population targeted (genetic)||Comments|
|Gamma Secretase Modulator/NSAID||Shifts amyloid beta production to shorter and less toxic species. Targets γ-secretase.||R-flurbiprofen (Flurizan, MPC-7869)||Phase III (completed)||Feb 2005||May 2008||1,600||Mild||n/a||Myriad Genetics concluded that the drug did not improve thinking ability or the ability of patients to carry out daily activities significantly more than those patients with placebo. They announced on June 30, 2008 that they would no longer be developing the drug|
|Gamma Secretase Inhibitor||Inhibits Gamma Secretase, which reduces amyloid beta levels||Semagacestat (LY450139)||Phase III (completed)||Sep 2008||Apr 2011||1,100||Mild-to-Moderate||n/a||On August 17, 2010, Eli Lilly announced that it would "halt development of semagacestat" as it "did not slow disease progression and was associated with worsening...cognition and the ability to perform activities of daily living." Also, it is "associated with an increased risk of skin cancer."|
|Antibody to amyloid beta||Mimics natural antibody triggered by AN-1792||Bapineuzumab (aab-001)||Phase III (completed)||Dec 2007||Apr 2012||1,121||Mild-to-Moderate||Apolipoprotein E4 Carriers only||On August 6, 2012, Pfizer and Johnson & Johnson said they are "ending development of an intravenous formulation" of bapineuzumab. Phase III trials "showed no treatment effect on either cognitive or functional outcomes. Biomarker analyses indicated that bapineuzumab engaged its target, but had no benefit."|
|Antibody to amyloid beta||Mimics natural antibody triggered by AN-1792||Bapineuzumab (aab-001)||Phase III (completed)||Dec 2007||Jun 2012||1,331||Mild-to-Moderate||Apolipoprotein E4 Non-Carriers only||On August 6, 2012, Pfizer and Johnson & Johnson said they are "ending development of an intravenous formulation" of bapineuzumab. Phase III trials "showed no treatment effect on either cognitive or functional outcomes. Biomarker analyses indicated that bapineuzumab engaged its target, but had no benefit."|
|Metal-Protein Interaction Attenuation||Primary targets are copper and zinc. Removes copper and zinc from cerebrospinal fluid.||PBT2 (8-hydroxy quinoline)||Phase II (completed)||Dec 2006||Dec 2007||80||Early Alzheimer's disease||n/a||"Did not meet its primary endpoint of a statistically significant reduction in the levels of beta-amyloid plaques in the brains prodromal/mild Alzheimer's disease patients." "No improvement was observed on the secondary endpoints of brain metabolic activity, cognition and function; however, there was a trend towards preserving hippocampal brain volume". "Specifically, there was less atrophy relative to the placebo group."|
|Fibrilization of amyloid beta||Breaks down neurotoxic fibrils, allowing amyloid peptides to clear the body rather than form amyloid plaques.||ELND005 (AZD-103, scyllo-Inositol)||Phase II (completed)||Dec 2007||May 2010||353||Mild-to-Moderate||n/a||Phase I produced encouraging results by August 2007. In December 2009, Elan and Transition jointly reported that the Phase II study has been modified so that only the 250 mg twice daily dose will be continued due to "greater rates of serious adverse events, including nine deaths," in the higher dose groups (1000 mg and 2000 mg dosed twice daily). It has received fast track designation from the U.S. FDA.|
|Neuroprotection||Neuroprotective Peptide, intra-nasal||AL-108||Phase II (completed)||Jan 2007||Jan 2008||120||Mild Cognitive Impairment||n/a||Deemed a Success; Phase III to start[dubious ]|
|Brain Cell Apoptosis Inhibitor||Operates through multiple mechanisms: Blocks the action of neurotoxic beta-amyloid proteins and inhibits L-type calcium channels, modulates the action of AMPA and NMDA glutamate receptors, may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, and blocks a number of other receptors, including α-adrenergic, 5-HT2C, 5-HT5A, and 5-HT6||latrepirdine (trade name: Dimebon)||Phase II (completed)||Sep 2006||Nov 2007 (actual)||183||Mild-to-Moderate||n/a||In March 2010, Pfizer announced that the Phase III CONNECTION trial failed to meet its primary and secondary endpoints. In January 2012, it was announced that the Phase III CONCERT study did not meet its co-primary endpoints. Both CONTACT and CONSTELLATION trials were terminated. Medivation and Pfizer discontinued development of dimebon and thus decided to end their co-development and marketing collaboration.|
|Natural Antibodies to amyloid beta||human plasma source limits supply||IVIg||Phase II (completed)||Feb 2006||June 2007||24||Mild-to-Moderate||n/a||Deemed a Success; Phase III to start|
|Vaccine to amyloid beta||Injects modified amyloid beta (active vaccine)||ACC-001||Phase II||Nov 2007||Mar 2012||228||Mild-to-Moderate||n/a||Sequel to famous AN-1792 Vaccine Trial|
The most widely used biomarker is the peptide beta-amyloid 1–42 (Aβ42), which is measured in cerebrospinal fluid. Levels of Aβ42 has a high agreement with beta-amyloid positron emission tomography (PET) and both methods detect prodromal AD with equally high accuracy.
Studies have also shown that people with AD had decreased glutamate (Glu) as well as decreased Glu/creatine (Cr), Glu/myo-inositol (mI), Glu/N-acetylaspartate (NAA), and NAA/Cr ratios compared to normal people. Both decreased NAA/Cr and decreased hippocampal glutamate may be an early indicator of AD.
Early research using a small cohort of Alzheimer's disease patients may have identified autoantibody markers for AD. The applicability of these markers is unknown.
A small human study in 2011 found that monitoring blood dehydroepiandrosterone (DHEA) variations in response to an oxidative stress could be a useful proxy test: the subjects with MCI did not have a DHEA variation, while the healthy controls did.
Positive preliminary results in rats with a non-invasive ultrasound technology aimed to clear the brain of amyloid plaques were reported in Science Translational Medicine. An Australian team describes the strategy as beaming ultrasound into the brain tissue. By oscillating at high frequencies, the sound waves combined with blood-borne microbubbles are able to open up the blood-brain barrier, so diminishing the brain defenses for some hours - an interval in which they stimulate the brain's microglial cells into activation (and, also, give drugs or the immune system access to the brain). The team reports having observed an important clearing out in the beta-amyloid clumps, a change attributed to the microglial cells since their function is basically connected with waste-removal; and full restoration of the lost memory and cognitive functions in 75 percent of the mice they tested it on, without concomitant damage to the brain parenchyma (either in the tissue that was surrounding the beta-amyloid plates, or elsewhere). The treated mice are reported to have displayed improved performance in three memory tasks – a maze, a test to make them to recognise new objects, and one to make them to remember the places they should avoid. On these results, the team is planning on starting trials with higher animal models, such as sheep and monkeys, for eventually to have human trials underway in 2017.
This section needs additional citations for verification. (March 2017) (Learn how and when to remove this template message)
Although in silico studies have advanced our understanding of Alzheimer's disease (AD) in many different areas, there are still limitations to these methodologies because bioinformatics tools are biased toward known data. Nonetheless, the findings obtained from using publicly available bioinformatics tools and databases have provided a mean to discover new treatments and to spark new questions to facilitate the process of finding cures for AD.
Pathogenesis and biomarkers
From gene expression patterns obtained in microarray datasets, correlation between cellular physiology and diseases can be revealed. Divergence studies (e.g. Jensen-Shannon divergence computations which interprets difference in gene expression and probability of distribution patterns) reveals gene expression distribution difference between AD and normal aging brains. That is, expressed genes that are negatively correlated with normal aging brain but are positively correlated with AD brains are possible biomarkers for AD diagnosis and treatment. Combining KEGG and PATHWAY studio, ATP5C1, COX6A1, NDUFV2, PLCB1, and PPP3CA are metabolism and mitochondrial-related genes that have been shown to be reduced in AD samples. Furthermore, metabolic dysregulations such as calcium homeostasis  and insulin signaling have also been identified to contribute to the onset of AD. Genes that are associated with calcium and insulin signaling are found using GATHER (online bioinformatics tool for analyzing genomic signatures). In fact, insulin signaling impairment and AD has been considered to be related in many levels. Functional protein sequence alignments (e.g. ClustalW, MUSCLE) and phylogenetic analysis (e.g. Phylip, Mega) demonstrate that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are highly linked in these two diseases. Increased BChE contributes altered lipoprotein metabolism and insulin insensitivity, and is positively correlated to hypertension and diabetes in correlation studies. AChE allows stabilization of neurotransmitter, acetylcholine (ACh), which is one of the main target for AD treatment. However, recent in silico pharmacological study examined drug-disease interaction showed that AChE inhibitors may not be the answer to AD treatment. PKC, ARG, HDAC, and GSK3 inhibitors that regulate calcium homeostasis and genetic modification of cell cycle and apoptosis may be the future targets of AD medication.
Neuronal plasticity is a key player in cognitive function that cannot be ignored in study of AD progression. Microarray studies found that NEFM, NEFL, and SV2B are highly downregulated in samples obtained from severe AD patients. NEFL is a neurofilament gene that has been shown to be related to hypotrophy of axons in motorneurons when mutated. However, both neurofilaments (NEFL and NEFM) have been documented to be involved in neurological disease, Charcot-Marie-Tooth, instead of AD, which demonstrate possible unknown connections of AD to other neurological diseases. SV2B is another gene that is downregulated in AD and has been shown to be related to neurodegeneration, particularly synaptic calcium-regulated exocytosis. The downregulation of genes responsible for neural synapse and neuroplasticity is related to another family of protein that has been found to be related to AD pathogenesis, EGR (early growth response). This EGR is regulated by upregulated FOXO1 (Forkhead Box O1) through PI3K/Akt pathway, which is listed as one of the pathway for future in anti-AD medication. These findings using computational methods allow for the connection of different studies and facilitate the understanding of disease complexity as well as directing to new possible biomarkers of AD.
The current treatment for AD symptoms are acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor (NMDA) antagonists. Based on the current literature on AD pharmacology research, analyzing differentially expressed genes in drug-drug, disease-disease, and drug-disease models allows the discovery of novel pharmaceutical agents that potentially treat more than AD symptoms. Analytical tools such as Connectivity Map (cMap) were used in drug-disease interaction from publicly available microarray data. Gene signatures from the cMap-based interpretation showed that common anti-AD drugs (tacrine, donepezil, galantamine, memantine, and rivastigmine) were not listed in the final drug list. Rather, other compounds that inhibit downstream effectors of cell proliferation, Wnt and insulin pathways, epigenetic modifications, and cell cycle regulation were among the top in the final anti-AD drug list. These findings further supported the fact that AD is a disease of degeneration and growth dysregulation. In fact, the final list of anti-AD drugs, obtained from analyzing microarray datasets and cMap drug-disease model contained the common effector of AD and diabetes – glycogen synthase kinase 3 (GSK3-an enzyme that has been found to be related to hyperphosphorylation of tau protein) – confirmed the link between the two diseases. Further pathway and network interpretation of genes obtained from AD microarray datasets using KEGG, WikiPathways, Reactome, Biocarta, and NetworkAnalyst showed that epidermal growth factor (EGF) and its receptors were strongly associated with pathogenesis of AD. EGFR is a transmembrane protein and a member of the HER/ErbB receptor family that share a common pathway with insulin receptors (Ras/Raf/Mak and PI3K/Akt). Furthermore, amyloid protein precursor (APP) was found to be indirectly related based on network analysis. Aβ (one of the diagnostic findings of AD) activates EGFR and inhibition of the receptor improved memory disorders in Aβ-overexpressed drosophila. Drugs that block GSK3 were found to be affecting PI3K/Akt pathway, demonstrating that EGFR could be a new target for pharmaceutical agent in treating AD.
- Underwood E (11 March 2015). "Ultrasound therapies target brain cancers and Alzheimer's disease". Science. doi:10.1126/science.aab0302.
- Dodel R, Neff F, Noelker C, Pul R, Du Y, Bacher M, Oertel W (March 2010). "Intravenous immunoglobulins as a treatment for Alzheimer's disease: rationale and current evidence". Drugs. 70 (5): 513–28. doi:10.2165/11533070-000000000-00000. PMID 20329802. Archived from the original on 2011-09-17. Retrieved 2010-03-27.
- Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM (May 2005). "Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial". Neurology. 64 (9): 1553–62. doi:10.1212/01.WNL.0000159740.16984.3C. PMID 15883316.
- Hawkes CA, McLaurin J (November 2007). "Immunotherapy as treatment for Alzheimer's disease". Expert Review of Neurotherapeutics. 7 (11): 1535–48. doi:10.1586/1473718.104.22.1685. PMID 17997702.
- Solomon B (June 2007). "Clinical immunologic approaches for the treatment of Alzheimer's disease". Expert Opinion on Investigational Drugs. 16 (6): 819–28. doi:10.1517/13543722.214.171.1249. PMID 17501694.
- Woodhouse A, Dickson TC, Vickers JC (2007). "Vaccination strategies for Alzheimer's disease: A new hope?". Drugs & Aging. 24 (2): 107–19. doi:10.2165/00002512-200724020-00003. PMID 17313199.
- Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA (July 2008). "Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial". Lancet. 372 (9634): 216–23. doi:10.1016/S0140-6736(08)61075-2. PMID 18640458.
- "Study Evaluating ACC-001 in Mild to Moderate Alzheimers Disease Subjects". Clinical Trial. FDA/clinicaltrials.gov. 2008-03-11.
- Kitazawa M, Vasilevko V, Cribbs DH, LaFerla FM (May 2009). "Immunization with amyloid-beta attenuates inclusion body myositis-like myopathology and motor impairment in a transgenic mouse model". The Journal of Neuroscience. 29 (19): 6132–41. doi:10.1523/JNEUROSCI.1150-09.2009. PMC 3049190. PMID 19439591. Lay summary.
Inclusion body myositis...features include T-cell mediated inflammatory infiltrates and aberrant accumulations of proteins, including amyloid-β (Aβ), tau, ubiquitinated proteins, apolipoprotein E, and β-synuclein in skeletal muscle. ... active immunization markedly reduces intracellular Aβ deposits and attenuates the motor impairment compared with untreated mice...Aβ oligomers contribute to the myopathy process as they were significantly reduced in the affected skeletal muscle from immunized mice. In addition, the anti-Aβ antibodies produced in the immunized mice blocked the toxicity of the Aβ oligomers in vitro, providing a possible key mechanism for the functional recovery.
- "Pfizer, J&J scrap Alzheimer's studies as drug fails". Reuters. 2012-08-07. Retrieved 2016-03-27.
- Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, Matcovitch-Natan O, Kertser A, David E, Amit I, Schwartz M (February 2016). "PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease". Nature Medicine. 22 (2): 135–7. doi:10.1038/nm.4022. PMID 26779813.
- "Lilly hit by spectacular failure of Phase III Alzheimer's candidate". PharmaTimes. August 18, 2010.
- Galasko DR, Graff-Radford N, May S, Hendrix S, Cottrell BA, Sagi SA, Mather G, Laughlin M, Zavitz KH, Swabb E, Golde TE, Murphy MP, Koo EH (2007). "Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals". Alzheimer Disease and Associated Disorders. 21 (4): 292–9. doi:10.1097/WAD.0b013e31815d1048. PMID 18090435.
- Eriksen JL, Sagi SA, Smith TE, Weggen S, Das P, McLendon DC, Ozols VV, Jessing KW, Zavitz KH, Koo EH, Golde TE (August 2003). "NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo". The Journal of Clinical Investigation. 112 (3): 440–9. doi:10.1172/JCI18162. PMC 166298. PMID 12897211.
- Christensen DD (February 2007). "Alzheimer's disease: progress in the development of anti-amyloid disease-modifying therapies". CNS Spectrums. 12 (2): 113–6, 119–23. PMID 17277711.
- Staff (1 October 2015). "Amgen and Novartis Collaborate on Neuroscience Drugs". News—Discovery & Development. Genetic Engineering & Biotechnology News (Paper). 35 (17). p. 14.
- Strozyk D, Launer LJ, Adlard PA, Cherny RA, Tsatsanis A, Volitakis I, Blennow K, Petrovitch H, White LR, Bush AI (July 2009). "Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid". Neurobiology of Aging. 30 (7): 1069–77. doi:10.1016/j.neurobiolaging.2007.10.012. PMC 2709821. PMID 18068270.
- Whitfield JF (October 2007). "The road to LOAD: late-onset Alzheimer's disease and a possible way to block it". Expert Opinion on Therapeutic Targets. 11 (10): 1257–60. doi:10.1517/14728126.96.36.1997. PMID 17907956.
- Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, Peskind ER, Raskind MA, Breitner JC, Montine TJ (August 2007). "Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease". Neurology. 69 (9): 878–85. doi:10.1212/01.wnl.0000277657.95487.1c. PMID 17724290.
- de la Monte SM, Tong M, Lester-Coll N, et al. (2006). "Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer's disease". Journal of Alzheimer's Disease. 10 (1): 89–109.
- de la Monte SM, Wands JR (November 2008). "Alzheimer's disease is type 3 diabetes-evidence reviewed". Journal of Diabetes Science and Technology. 2 (6): 1101–13. doi:10.1177/193229680800200619. PMC 2769828. PMID 19885299.
- Marx CE, Trost WT, Shampine LJ, Stevens RD, Hulette CM, Steffens DC, Ervin JF, Butterfield MI, Blazer DG, Massing MW, Lieberman JA (December 2006). "The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease". Biological Psychiatry. 60 (12): 1287–94. doi:10.1016/j.biopsych.2006.06.017. PMID 16997284.
- Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, Thompson RF, Brinton RD (April 2010). "Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 107 (14): 6498–503. Bibcode:2010PNAS..107.6498W. doi:10.1073/pnas.1001422107. PMC 2851948. PMID 20231471.
- "Angiotensin receptor blockers are lower incidence, progression of Alzheimer's disease"
- Choi Y, Kim HS, Shin KY, Kim EM, Kim M, Kim HS, Park CH, Jeong YH, Yoo J, Lee JP, Chang KA, Kim S, Suh YH (November 2007). "Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models". Neuropsychopharmacology. 32 (11): 2393–404. doi:10.1038/sj.npp.1301377. PMID 17406652.
- Hunter CL, Quintero EM, Gilstrap L, Bhat NR, Granholm AC (June 2004). "Minocycline protects basal forebrain cholinergic neurons from mu p75-saporin immunotoxic lesioning". The European Journal of Neuroscience. 19 (12): 3305–16. doi:10.1111/j.0953-816X.2004.03439.x. PMID 15217386.
- Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen JC, Jenkins NA, Copeland NG, Younkin LH, Lester HA, Younkin SG, Borchelt DR (December 2005). "Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease". PLoS Medicine. 2 (12): e355. doi:10.1371/journal.pmed.0020355. PMC 1283364. PMID 16279840.
- Khlistunova I, Biernat J, Wang Y, Pickhardt M, von Bergen M, Gazova Z, Mandelkow E, Mandelkow EM (January 2006). "Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs". The Journal of Biological Chemistry. 281 (2): 1205–14. doi:10.1074/jbc.M507753200. PMID 16246844.
- http://clinicaltrials.gov/ct2/results?term=antibiotic&recr=&rslt=&type=&cond=%22Alzheimer+Disease%22&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s=&lup_e= clinicaltrials.gov
- Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, Smith S, Borrie M, Decoteau E, Davidson W, McDougall A, Gnarpe J, O'DONNell M, Chernesky M (March 2004). "A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease". Journal of the American Geriatrics Society. 52 (3): 381–7. doi:10.1111/j.1532-5415.2004.52109.x. PMID 14962152.
- Carusone SC, Goldsmith CH, Smieja M, Loeb M (April 2006). "Summary measures were a useful alternative for analyzing therapeutic clinical trial data". Journal of Clinical Epidemiology. 59 (4): 387–92. doi:10.1016/j.jclinepi.2005.05.009. PMID 16549261.
- Molloy DW, Standish TI, Zhou Q, Guyatt G (May 2013). "A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial". International Journal of Geriatric Psychiatry. 28 (5): 463–70. doi:10.1002/gps.3846. PMID 22718435.
- Wozniak MA, Mee AP, Itzhaki RF (January 2009). "Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques". The Journal of Pathology. 217 (1): 131–8. doi:10.1002/path.2449. PMID 18973185.
- "Cannabis and dementia". Alzheimer's Society. 2018. Retrieved 2018-10-23.
- Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, Seely L, Hung D (July 2008). "Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study". Lancet. 372 (9634): 207–15. doi:10.1016/S0140-6736(08)61074-0. PMID 18640457.
- Dimebon Disappoints in Phase 3 Trial
- "Pfizer And Medivation Announce Results From Two Phase 3 Studies In Dimebon (latrepirdine*) Alzheimer's Disease Clinical Development Program" (Press release). Business Wire. 3 March 2010. Archived from the original on 4 September 2012.
- Holmes, C.; Cunningham, C.; Zotova, E.; Woolford, J.; Dean, C.; Kerr, S.; Culliford, D.; Perry, V. H. (2009-09-08). "Systemic inflammation and disease progression in Alzheimer disease". Neurology. 73 (10): 768–774. doi:10.1212/WNL.0b013e3181b6bb95. ISSN 0028-3878. PMC 2848584. PMID 19738171.
- Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S (November 2005). "Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study". The American Journal of Geriatric Psychiatry. 13 (11): 950–8. doi:10.1176/appi.ajgp.13.11.950. PMID 16286438.
- Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, Zvartau-Hind ME, Hosford DA, Roses AD (2006). "Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease". The Pharmacogenomics Journal. 6 (4): 246–54. doi:10.1038/sj.tpj.6500369. PMID 16446752.
- Brodbeck J, Balestra ME, Saunders AM, Roses AD, Mahley RW, Huang Y (January 2008). "Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons". Proceedings of the National Academy of Sciences of the United States of America. 105 (4): 1343–6. Bibcode:2008PNAS..105.1343B. doi:10.1073/pnas.0709906104. PMC 2234140. PMID 18212130.
- "Alzheimer's 'is brain diabetes'". BBC News. 2009-02-03.[unreliable medical source?]
- Freiherr J, Hallschmid M, Frey WH, Brünner YF, Chapman CD, Hölscher C, Craft S, De Felice FG, Benedict C (July 2013). "Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence". CNS Drugs. 27 (7): 505–14. doi:10.1007/s40263-013-0076-8. PMC 3709085. PMID 23719722.
- Vandal M, White PJ, Tremblay C, St-Amour I, Chevrier G, Emond V, Lefrançois D, Virgili J, Planel E, Giguere Y, Marette A, Calon F (December 2014). "Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease". Diabetes. 63 (12): 4291–301. doi:10.2337/db14-0375. PMID 25008180.
- Wischik CM, Bentham P, Wischik DJ, Seng KM (July 2008). "Tau aggregation inhibitor (TAI) therapy with Rember arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks". Alzheimer's & Dementia. 4 (4S): T167. doi:10.1016/j.jalz.2008.05.438.
- Bulic B, Pickhardt M, Schmidt B, Mandelkow EM, Waldmann H, Mandelkow E (2009). "Development of tau aggregation inhibitors for Alzheimer's disease" (PDF). Angewandte Chemie. 48 (10): 1740–52. doi:10.1002/anie.200802621. PMID 19189357.
- "Sigma Receptors". Anavex Life Sciences Corporation. Archived from the original on 2012-02-16. Retrieved June 27, 2012.
- Maurice T, Su TP (November 2009). "The pharmacology of sigma-1 receptors". Pharmacology & Therapeutics. 124 (2): 195–206. doi:10.1016/j.pharmthera.2009.07.001. PMC 2785038. PMID 19619582.
- "Researchers Closer to Alzheimer's Prevention, Treatment". Bioscience Technology. 2013-05-22. Retrieved 2013-05-26.
- Barron AM, Garcia-Segura LM, Caruso D, Jayaraman A, Lee JW, Melcangi RC, Pike CJ (May 2013). "Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease". The Journal of Neuroscience. 33 (20): 8891–7. doi:10.1523/JNEUROSCI.1350-13.2013. PMC 3733563. PMID 23678130.
- Liu C, Chan CB, Ye K (2016). "7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders". Translational Neurodegeneration. 5 (1): 2. doi:10.1186/s40035-015-0048-7. PMC 4702337. PMID 26740873.
- Kazim SF, Iqbal K (July 2016). "Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease". Molecular Neurodegeneration. 11 (1): 50. doi:10.1186/s13024-016-0119-y. PMC 4940708. PMID 27400746.
- "Efficacy Study of MPC-7869 to Treat Patients With Alzheimer's". Clinical Trial. FDA/clinicaltrials.gov. 2005-03-15.
- "Myriad Genetics Reports Results of U.S. Phase 3 Trial of Flurizan™ in Alzheimer's Disease". Myriad Genetics. 2008-06-30. Archived from the original on July 30, 2008.
- "Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo (IDENTITY-2)". Clinical Trial. FDA/clinicaltrials.gov. 2008-09-26.
- "Lilly Halts Development of Semagacestat for Alzheimer's Disease Based on Preliminary Results of Phase III Clinical Trials". investor.lilly.com. 2010-08-17.
- "Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease (ApoE4 Carrier)". Clinical Trial. FDA/clinicaltrials.gov.
- "J&J, Pfizer to drop intravenous Alzheimer's drug". businessweek.com. 2012-08-06.
- "Bapineuzumab". alzforum.org.
- "Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease (ApoE4 Non-Carrier)". Clinical Trial. FDA/clinicaltrials.gov.
- "Study Evaluating the Safety, Tolerability and Efficacy of PBT2 in Patients With Early Alzheimer's Disease". Clinical Trial. FDA/clinicaltrials.gov.
- "Prana Biotechnology announces preliminary results of Phase 2 IMAGINE trial of PBT2 in Alzheimer's disease" (Press release). Prana Biotechnology. prnewswire.com.
- "ELND005 in Patients With Mild to Moderate Alzheimer's Disease". Clinical Trial. FDA/clinicaltrials.gov. 2011-09-27.
- "RPT-UPDATE 2-Elan, Transition drop top drug doses after deaths". Reuters. reuters.com. 2009-12-15.
- "FDA Grant Fast Track Designation to ELND005 for the Treatment of Neuropsychiatric Symptoms in Alzheimer's Disease" (Press release). Transition Therapeutics Inc. prnewswire.com.
- "Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment". Clinical Trial. FDA/clinicaltrials.gov. 2008-03-11.
- Lermontova NN, Redkozubov AE, Shevtsova EF, Serkova TP, Kireeva EG, Bachurin SO (November 2001). "Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels". Bulletin of Experimental Biology and Medicine. 132 (5): 1079–83. doi:10.1023/A:1017972709652. PMID 11865327.
- Grigorev VV, Dranyi OA, Bachurin SO (November 2003). "Comparative study of action mechanisms of dimebon and memantine on AMPA- and NMDA-subtypes glutamate receptors in rat cerebral neurons". Bulletin of Experimental Biology and Medicine. 136 (5): 474–7. doi:10.1023/B:BEBM.0000017097.75818.14. PMID 14968164.
- Bachurin SO, Shevtsova EP, Kireeva EG, Oxenkrug GF, Sablin SO (May 2003). "Mitochondria as a target for neurotoxins and neuroprotective agents". Annals of the New York Academy of Sciences. 993 (1): 334–44, discussion 345–9. Bibcode:2003NYASA.993..334B. doi:10.1111/j.1749-6632.2003.tb07541.x. PMID 12853325.
- Wu J, Li Q, Bezprozvanny I (October 2008). "Evaluation of Dimebon in cellular model of Huntington's disease" (PDF). Molecular Neurodegeneration. 3: 15. doi:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.
- "Double-Blind, Placebo-Controlled Study of Oral Dimebon in Subjects With Mild to Moderate Alzheimer's Disease". Clinical Trial. FDA/clinicaltrials.gov. 2007-12-27.
- "Pfizer And Medivation Announce Results From Two Phase 3 Studies In Dimebon (latrepirdine*) Alzheimer's Disease Clinical Development Program". medivation.com. 2010-03-03. Archived from the original on 2012-09-04.
- "Medivation and Pfizer Announce Results from Phase 3 Concert Trial of Dimebon in Alzheimer's Disease". medivation.com. 2012-01-17.
- "Pfizer, Medivation Nix Development of Alzheimer Disease Therapy". genengnews.com. 2012-01-17.
- "Phase II Study of Intravenous Immunoglobulin (IVIg) for Alzheimer's Disease". Clinical Trial. FDA/clinicaltrials.gov. 2007-08-03.
- Blennow K, Hampel H, Weiner M, Zetterberg H (March 2010). "Cerebrospinal fluid and plasma biomarkers in Alzheimer disease". Nature Reviews. Neurology. 6 (3): 131–44. doi:10.1038/nrneurol.2010.4. PMID 20157306.
- Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, Owenius R, Hägerström D, Wollmer P, Minthon L, Hansson O (October 2014). "Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid β-amyloid 42: a cross-validation study against amyloid positron emission tomography". JAMA Neurology. 71 (10): 1282–9. doi:10.1001/jamaneurol.2014.1358. PMID 25155658.
- Palmqvist S, Zetterberg H, Mattsson N, Johansson P, Minthon L, Blennow K, Olsson M, Hansson O (October 2015). "Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease". Neurology. 85 (14): 1240–9. doi:10.1212/WNL.0000000000001991. PMC 4607601. PMID 26354982.
- Reduced Hippocampal Glutamate in Alzheimer Disease. Neurobiol Aging. 2009;32(5):802–810. doi:10.1016/j.neurobiolaging.2009.05.002. PMID 19501936.(primary source)
- Identification of Candidate IgG Antibody Biomarkers for Alzheimer's Disease Through Screening of Synthetic Combinatorial Libraries. Cell. 2011;144(1):132–42. doi:10.1016/j.cell.2010.11.054. PMID 21215375. (primary source)
- A Lead Study on Oxidative Stress-mediated Dehydroepiandrosterone Formation in Serum: The Biochemical Basis for a Diagnosis of Alzheimer's Disease. J Alzheimers Dis. 2011-01-01;24(1):5–16. doi:10.3233/JAD-2011-101941. PMID 21335661. (primary source)
- Leidinger P, Backes C, Deutscher S, Schmitt K, Mueller SC, Frese K, Haas J, Ruprecht K, Paul F, Stähler C, Lang CJ, Meder B, Bartfai T, Meese E, Keller A (July 2013). "A blood based 12-miRNA signature of Alzheimer disease patients". Genome Biology. 14 (7): R78. doi:10.1186/gb-2013-14-7-r78. PMC 4053778. PMID 23895045.
- Leinenga G, Götz J (March 2015). "Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer's disease mouse model". Science Translational Medicine. 7 (278): 278ra33. doi:10.1126/scitranslmed.aaa2512. PMID 25761889.
- Li Di; Edward H. Kerns (2015). Blood-Brain Barrier in Drug Discovery: Optimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects for Peripheral Drugs. Wiley. pp. 1–4, 521–579. ISBN 978-1118788356.
- Underwood E (March 2015). "Neuroscience. Can sound open the brain for therapies?". Science. 347 (6227): 1186–7. doi:10.1126/science.347.6227.1186. PMID 25766212.
- Götz, Jürgen. "Radio Interview, "16 March 2015 on Health Report"". ABC Radio (Australia). Retrieved March 23, 2015.
- Gómez Ravetti M, Rosso OA, Berretta R, Moscato P (April 2010). "Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease". PLOS One. 5 (4): e10153. Bibcode:2010PLoSO...510153G. doi:10.1371/journal.pone.0010153. PMC 2854141. PMID 20405009.
- Ongwijitwat S, Wong-Riley MT (August 2004). "Functional analysis of the rat cytochrome c oxidase subunit 6A1 promoter in primary neurons". Gene. 337: 163–71. doi:10.1016/j.gene.2004.04.024. PMID 15276212.
- Washizuka S, Iwamoto K, Kakiuchi C, Bundo M, Kato T (March 2009). "Expression of mitochondrial complex I subunit gene NDUFV2 in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia". Neuroscience Research. 63 (3): 199–204. doi:10.1016/j.neures.2008.12.004. PMID 19135101.
- Spires TL, Molnár Z, Kind PC, Cordery PM, Upton AL, Blakemore C, Hannan AJ (April 2005). "Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling". Cerebral Cortex. 15 (4): 385–93. doi:10.1093/cercor/bhh141. PMID 15749982.
- Tiveci S, Akin A, Cakir T, Saybaşili H, Ulgen K (April 2005). "Modelling of calcium dynamics in brain energy metabolism and Alzheimer's disease". Computational Biology and Chemistry. 29 (2): 151–62. doi:10.1016/j.compbiolchem.2005.03.002. PMID 15833443.
- Sánchez-Chávez G, Salceda R (April 2000). "Effect of streptozotocin-induced diabetes on activities of cholinesterases in the rat retina". IUBMB Life. 49 (4): 283–7. doi:10.1080/15216540050033140. PMID 10995030.
- Alcântara VM, Chautard-Freire-Maia EA, Scartezini M, Cerci MS, Braun-Prado K, Picheth G (2002-01-01). "Butyrylcholinesterase activity and risk factors for coronary artery disease". Scandinavian Journal of Clinical and Laboratory Investigation. 62 (5): 399–404. doi:10.1080/00365510260296564. PMID 12387587.
- Siavelis JC, Bourdakou MM, Athanasiadis EI, Spyrou GM, Nikita KS (March 2016). "Bioinformatics methods in drug repurposing for Alzheimer's disease". Briefings in Bioinformatics. 17 (2): 322–35. doi:10.1093/bib/bbv048. PMID 26197808.
- Dubois M, Lalonde R, Julien JP, Strazielle C (June 2005). "Mice with the deleted neurofilament of low-molecular-weight (Nefl) gene: 1. Effects on regional brain metabolism". Journal of Neuroscience Research. 80 (6): 741–50. doi:10.1002/jnr.20449. PMID 15742362.
- Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, Martin JJ, Butler IJ, Mancias P, Papasozomenos SC, Terespolsky D, Potocki L, Brown CW, Shy M, Rita DA, Tournev I, Kremensky I, Lupski JR, Timmerman V (March 2003). "Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease". Brain. 126 (Pt 3): 590–7. doi:10.1093/brain/awg059. PMID 12566280.
- Lus G, Nelis E, Jordanova A, Löfgren A, Cavallaro T, Ammendola A, Melone MA, Rizzuto N, Timmerman V, Cotrufo R, De Jonghe P (October 2003). "Charcot-Marie-Tooth disease with giant axons: a clinicopathological and genetic entity". Neurology. 61 (7): 988–90. doi:10.1212/wnl.61.7.988. PMID 14557576.
- Heese K, Nagai Y, Sawada T (August 2002). "The 3' untranslated region of the new rat synaptic vesicle protein 2B mRNA transcript inhibits translational efficiency". Brain Research. Molecular Brain Research. 104 (2): 127–31. doi:10.1016/s0169-328x(02)00326-1. PMID 12225865.
- MacGibbon GA, Lawlor PA, Walton M, Sirimanne E, Faull RL, Synek B, Mee E, Connor B, Dragunow M (October 1997). "Expression of Fos, Jun, and Krox family proteins in Alzheimer's disease". Experimental Neurology. 147 (2): 316–32. doi:10.1006/exnr.1997.6600. PMID 9344557.
- Cabodi S, Morello V, Masi A, Cicchi R, Broggio C, Distefano P, Brunelli E, Silengo L, Pavone F, Arcangeli A, Turco E, Tarone G, Moro L, Defilippi P (February 2009). "Convergence of integrins and EGF receptor signaling via PI3K/Akt/FoxO pathway in early gene Egr-1 expression". Journal of Cellular Physiology. 218 (2): 294–303. doi:10.1002/jcp.21603. PMID 18844239.
- Forde JE, Dale TC (August 2007). "Glycogen synthase kinase 3: a key regulator of cellular fate". Cellular and Molecular Life Sciences. 64 (15): 1930–44. doi:10.1007/s00018-007-7045-7. PMID 17530463.
- Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW (March 2003). "Epidermal growth factor receptor: mechanisms of activation and signalling". Experimental Cell Research. 284 (1): 31–53. doi:10.1016/s0014-4827(02)00098-8. PMID 12648464.
- Siddiqui S, Fang M, Ni B, Lu D, Martin B, Maudsley S (2012-01-01). "Central role of the EGF receptor in neurometabolic aging". International Journal of Endocrinology. 2012: 1–14. doi:10.1155/2012/739428. PMC 3382947. PMID 22754566.
- Wang L, Chiang HC, Wu W, Liang B, Xie Z, Yao X, Ma W, Du S, Zhong Y (October 2012). "Epidermal growth factor receptor is a preferred target for treating amyloid-β-induced memory loss". Proceedings of the National Academy of Sciences of the United States of America. 109 (41): 16743–8. doi:10.1073/pnas.1208011109. PMC 3478595. PMID 23019586.