Jump to content

User:WikiDan61/LATE

From Wikipedia, the free encyclopedia
< User:WikiDan61

This is the current revision of this page, as edited by WhatamIdoing (talk | contribs) at 01:43, 9 July 2024 (Reference formatting). The present address (URL) is a permanent link to this version.

(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)
LATE neuropathologic changes (LATE-NC). A normal centenarian brain, cut in the coronal plane (top left) is compared to a brain with LATE-NC (top right). The hippocampi on both sides are atrophic (shrunken) in the brain with LATE-NC. The bottom 3 panels show photomicrographs of a hippocampus with LATE-NC, stained for phosphorylated TDP-43 protein (TDP-43). Insets show TDP-43 positive neuronal cytoplasmic inclusions (Inset A--in dentate granule cells) and wispy non-tapering cellular processes stained for TDP-43 protein (Inset B--in CA1).

Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE)

Limbic-predominant Age-related TDP-43 Encephalopathy, commonly abbreviated as LATE, is a neurodegenerative disease that affects persons of advanced age, usually beyond age 80 years.[1] LATE is a common contributor to the clinical syndrome that is called dementia.

In terms of symptoms, LATE mimics Alzheimer's disease. Unlike Alzheimer's disease, which is associated with microscopic brain lesions called amyloid-beta plaques and tau protein neurofibrillary tangles,[2] LATE by definition involves microscopic lesions made up of a distinct protein called TDP-43.[1] In LATE, these microscopic TDP-43 protein deposits primarily impact the medial temporal lobe, a brain region that includes anatomical structures critical for memory.[1]

LATE is a very common disease among the elderly, impacting approximately one-third of individuals over the age of 85 years.[3] As therapeutic strategies evolve, especially for Alzheimer's disease, distinguishing LATE becomes even more pivotal to tailor interventions effectively (for both LATE and Alzheimer's disease) and to improve overall health in the geriatric population.

Classification

[edit]

LATE is a neurodegenerative disorder predominantly characterized by the pathological misfolding and aggregation of the protein called TDP-43 (TAR-DNA binding protein of 43 kilodalton), within specific areas of the brain.[1] LATE occurs with increasing frequency in persons beyond 85 years of age, reaching highest prevalence in the oldest old.[1]  LATE is distinct from other neurodegenerative diseases such as Alzheimer's Disease and frontotemporal dementia (FTD). The primary distinction lies in the predominant protein pathology, and the localization of that pathology: whereas Alzheimer's disease involves amyloid-beta plaques and tau protein tangles,[2] and FTD is often linked to TDP-43 pathology that is very widespread in the brain,[4] LATE is defined by TDP-43 deposited in a more restricted distribution within the brain.

LATE is subcategorized under the umbrella of TDP-43 proteinopathies, which also include conditions like frontotemporal lobar degeneration (FTLD)/FTD and amyotrophic lateral sclerosis (ALS) where TDP-43 was discovered as a pathological marker,[5] indicating a common pathological protein despite distinct neuroanatomical and clinical findings. LATE primarily affects the medial temporal lobe regions, particularly the hippocampus and amygdala, which are crucial for memory functions. This localization correlates with clinical presentation as a predominantly amnestic (memory-impacting) condition, which is often mistaken for Alzheimer's disease.

LATE's classification is also nuanced by its high potential to coexist with other neuropathological conditions. Autopsy studies frequently reveal the coexistence of LATE neuropathologic changes (LATE-NC) with Alzheimer's disease neuropathologic changes (ADNC).[6][7] and other pathologies such as vascular brain injury [8] This overlap can complicate diagnosis and treatment, emphasizing the importance of accurate classification and understanding of its unique and intersecting features within the neurodegenerative disease spectrum.[9] Understanding these relationships is crucial for developing targeted treatments and improving diagnostic accuracy for aging populations.

In terms of nomenclature, the acronym LATE stands for Limbic-predominant Age-related TDP-43 Encephalopathy: “limbic” is related to the brain areas first involved, “age-related” indicates that this is a disease that increases in the geriatric population,[1] “TDP-43” indicates the aberrant mis-folded protein (or proteinopathy) deposits in the brain that characterize LATE, and “encephalopathy” means illness of brain.  A connotation of the acronym “LATE” is that the designation refers to the onset of disease usually in persons aged 80 or older, i.e. late in the human aging spectrum.

Signs and symptoms

[edit]

LATE is associated with a range of clinical symptoms that primarily affect cognitive functions, particularly memory.[10] The clinical signs and symptoms of LATE closely mimic those of Alzheimer's disease, often leading to diagnostic challenges.[11]

Cognitive symptoms

[edit]

The hallmark symptom of LATE is a progressive memory loss that predominantly affects short-term and episodic memory.[1] This impairment is often severe enough to interfere with daily functioning and usually remains the chief neurologic deficit, unlike other types of dementia in which non-memory cognitive domains and behavioral changes might be noted earlier or more prominently.[10] The amnestic syndrome in LATE tends to worsen gradually, leading to significant memory deficits over time.  Unlike more rapidly progressive dementias, the cognitive decline in LATE, when it is the chief pathology present is typically slow. [12]

The term dementia refers to a clinical syndrome, rather than a particular disease process – it can be caused by many different subtypes of brain disease, which often occur in combination with each other.  Thus, many different diseases including LATE contribute to dementia. The implications of the term dementia are that there is cognitive impairment severe enough to impair activities of daily living such as feeding oneself.[13] Approximately half of dementia in advanced age includes both Alzheimer's disease and LATE pathologies, and these individuals are at risk for more swift and severe disease course.[2][14]

Combinations of brain pathology, and their correlation with cognitive impairment over time. Note that the combination of AD+LATE is the most common and most severe.

Behavioral and psychological symptoms

[edit]

Individuals with LATE may experience mood swings, depression, and apathy.[15] These symptoms can complicate the clinical picture, especially in the elderly who may have other comorbid conditions affecting their mood and cognitive status.  Neuropsychological disturbances are particularly common when LATE is combined with Alzheimer's disease. There can be subtle changes in personality and behavior. Family members may notice less social interaction, and a general withdrawal from previously enjoyed activities.

Development and progression

[edit]

The symptoms of “Pure” LATE develop more insidiously than those of Alzheimer's disease.[12] Initial symptoms are often so mild that they are dismissed as normal aging. However, as the disease progresses, memory impairment becomes more prominent and begins to interfere significantly with daily activities. The rate of progression varies widely among individuals but generally occurs over several years.  Again, it should be emphasized that up to ½ of dementia in advanced age involves both Alzheimer's and LATE pathologies, and affected individuals with so-called “mixed” pathologies have more rapid and severe disease course.[12]

Causes

[edit]

The exact causes of LATE are not fully understood, but a combination of factors, particularly genetic risk factors, are believed to contribute to its development. Here we explore these factors based on current research and theories.

Genetic factors

[edit]

The major known risk factors for LATE-NC are genetic: variations in the TMEM106B, GRN, APOE, ABCC9, KCNMB2, and WWOX genes have been linked to altered risk for LATE-NC (and/or hippocampal sclerosis dementia).[16][17][18][19][20][21][22]

Risk factors

[edit]

The strongest known risk factor for LATE is advanced age. The prevalence of LATE increases significantly in individuals over 80 years old [23][24] and the average patient with LATE is ten years older than the average patient with Alzheimer's disease, suggesting that aging-related biological processes—yet to be comprehensively identified (but which include TMEM106B c-terminal fragments),[25] -- play roles in the development of LATE. Although brain trauma (either single or multiple/chronic traumatic impacts) can produce brain changes that are qualitatively different from LATE-NC[26] there may be interactions between brain trauma and LATE-NC mechanistically.  Further, those with brain damage from trauma or other sources may have worse outcomes with a given burden of LATE-NC in the brain. There is indication from broader dementia research that higher educational attainment and engaging in mentally stimulating activities might delay the onset of clinical symptoms in neurodegenerative diseases.[27] Whether this directly affects the risk of developing LATE or just modifies its presentation is still under investigation. While specific lifestyle factors directly causing LATE have not been definitively identified, general factors that affect brain health appear to influence risk of a given amount of pathology being correlated with cognitive impairment. Lifestyle factors include diet, physical activity, social and intellectual stimulation, cardiovascular health, and exposure to toxins. Chronic inflammation in the brain is a known factor in many neurodegenerative diseases and may also play a role in LATE. Inflammatory processes could contribute to or exacerbate TDP-43 pathology.[28] Disruptions in protein homeostasis, which include protein synthesis, folding, trafficking, and degradation, are likely involved in LATE.[29] An imbalance in these processes could lead to the accumulation of misfolded TDP-43, contributing to disease progression.

Pathophysiology

[edit]

TDP-43 (Transactive response DNA-binding protein) is a nuclear protein involved in regulating gene expression by modifying RNA. It plays critical roles in RNA processing, including splicing, stability, and transport.[30] In healthy cells, TDP-43 is predominantly found in the nucleus. In LATE, TDP-43 protein abnormally accumulates in the cytoplasm of neurons and glial cells, forming aggregates. This cellular mislocalization disrupts its normal nuclear functions and contributes to cellular dysfunction and neuronal death.[29] The exact triggers of TDP-43 aggregation are not fully understood but are believed to involve both genetic predispositions and acquired factors.[31]

LATE neuropathology is typically graded based on the extent and distribution of TDP-43 inclusions within the brain.Cite error: The <ref> tag has too many names (see the help page). Early stages may involve localized TDP-43 pathology in the amygdala, while more advanced stages involve the hippocampus and other medial temporal lobe structures, whereas in more advanced disease the TDP-43 pathology is far more extensive.Cite error: The <ref> tag has too many names (see the help page). For more details on the pathological stages of LATE-NC, see “Pathologic Examination”, below.

Advanced LATE is often associated with hippocampal sclerosis, characterized by severe neuron loss and gliosis in the hippocampus.[32] This feature significantly contributes to the memory deficits observed in LATE.[33][34][35] LATE often coexists with a small blood vessel pathology affecting cerebral arterioles, which is termed arteriolosclerosis.[36] LATE is more common in cases with comorbid tauopathy, including ADNC, primary age-related tauopathy (PART), and age-related tau astrogliopathy.[8]

Certain genetic factors, such as mutations or polymorphisms in genes related to TDP-43 processing and function, may predispose individuals to develop LATE. These genetic elements can affect the stability, aggregation propensity, or cellular trafficking of TDP-43. For example, the APOE e4 allele that confers increased risk for ADNC also increases risk of LATE-NC;[22] further, FTLD risk genes TMEM106B and GRN/progranulin are also implicated in risk of LATE-NC.[8]

Diagnosis

[edit]

The diagnosis of LATE is challenging because its symptoms overlap with those of other types of dementia, especially Alzheimer's disease.[37] At present LATE is primarily diagnosed posthumously, through neuropathological examination. However, ongoing research aims to refine the antemortem diagnostic criteria and methods. The current approach to diagnosing LATE in living patients involves a combination of clinical evaluation, neuroimaging, and biomarker analysis, as detailed below.

Clinical evaluation

[edit]

Detailed patient history focusing on age at onset and nature and rate of decline of cognitive functions, particularly memory loss, is critical. Clinicians also assess other cognitive domains and inquire about any changes in behavior or personality that might indicate broader neurological impact. Neuropsychologic examinations include testing to assess memory, executive function, language abilities, and other cognitive functions. These tests help differentiate LATE from other neurodegenerative diseases based on the presence of primarily amnestic versus multi-domain cognitive impairments.

MRI (coronal plane) showing patient with eventually autopsy-proven LATE neuropathology

MRI scans are used to observe structural changes in the brain. In LATE, MRI may reveal severe atrophy in the medial temporal lobe, particularly in the hippocampus and amygdala, which are key areas affected by TDP-43 pathology, and may indicate hippocampal sclerosis.[11][6][38][39][40] Other MRI abnormalities have recently been also observed in association with LATE.[41][42] While PET scans are commonly used to detect amyloid and tau pathologies in Alzheimer's disease, the absence of marked aberration in these may support the diagnosis of LATE by ruling out significant amyloid or tau burdens indicative of Alzheimer's disease.

Biomarkers for neuronal damage such as tau protein and neurofilaments can be measured in the cerebrospinal fluid and blood.[43][44] A lack of amyloid-beta and tau relative to the degree of cognitive impairment may suggest LATE, if typical Alzheimer's pathology is not present. Vigorous efforts are ongoing to identify specific biomarkers for TDP-43 pathology.[45] These include potential CSF markers or blood-based biomarkers derived from advanced protein assays, which could specifically indicate the presence of abnormal TDP-43.

Pathological examination

[edit]

Definitive diagnosis of LATE currently relies on post-mortem examination, where brain tissues are examined for specific patterns of TDP-43 proteinopathy. The distribution and severity of TDP-43 inclusions, especially in the amygdala and hippocampus, confirm the presence of LATE. The specific severity/extent of LATE-NC follows on the basic staging scheme[1] based on a stereotypic expansion of TDP-43 pathology in the aged brain. This pattern was originally identified Keith Josephs and colleagues.[46][47] and was later corroborated by Dr. Julie Schneider and colleagues at Rush University Medical Center. [48] For routine LATE-NC diagnosis, the pathology is staged along a 0-3 staging scheme:[1][49] when TDP-43 pathology is only seen in the amygdala, that is LATE-NC Stage 1; when TDP-43 pathology is in the amygdala and hippocampus, that is LATE-NC Stage 2; and, when TDP-43 pathology is in amygdala, hippocampus, and middle frontal gyrus, that is LATE-NC Stage 3. 

Prognosis

[edit]

The prognosis of LATE varies significantly depending on several factors including the age at onset, stage of the disease at diagnosis, the presence and degree of cerebrovascular disease and of other comorbidities, and individual patient factors. Understanding the progression, expected outcomes, and influencing factors is crucial for managing LATE effectively and providing appropriate care and support to affected individuals and their families.

LATE typically manifests as a slow, progressive decline in memory and other cognitive functions,[50] which distinguishes it from more rapidly progressing forms of dementia. The rate of progression can vary widely among individuals. Early stages may involve subtle memory impairments that gradually worsen.[50] As LATE progresses, patients may experience more significant memory loss and eventually exhibit symptoms affecting other cognitive domains, although the primary impairment usually remains in memory. Progression to severe dementia is common, and as with many forms of dementia, individuals with LATE gradually require more assistance with daily activities, leading to significant dependency on caregivers.

Epidemiology

[edit]

LATE is an increasingly recognized neurodegenerative condition and the prevalence is highest in the “oldest-old” (those beyond age 85 years)[3] Studies suggest that LATE neuropathological changes are present in >30% of individuals older than 85 years,[3][51] making it one of the more common dementia-associated conditions in the elderly. LATE often coexists with other common brain pathologies of aging, such as Alzheimer's disease and/or cerebrovascular disorder. The risk of developing LATE increases with age, being unusual in individuals under 65 and increasingly common in those over 80.[24][52] Studies have not shown consistent differences between males and females in the prevalence of LATE. Limited data are available on the prevalence of LATE across different ethnic and racial groups.[53][54] Initial studies have not indicated significant differences in prevalence based on race or ethnicity. LATE has been identified in populations studied around the world.[3] However, differences in study designs, diagnostic criteria, and awareness of the disease may affect reported rates from different countries. The recognition and reporting of LATE may also vary significantly depending on the local healthcare system's capacity to diagnose and record cases of dementia, particularly in settings where detailed neuropathological examinations are less common. Understanding the true epidemiological impact of LATE is essential for planning of research, healthcare, and resource allocation, especially as populations age.

History

[edit]

The pathological signatures of the disorder now known as LATE have been observed at least since the mid-1990s,[55] but attention on the TDP-43 protein that is part of its mechanism have been relatively recent. TDP-43 was first linked to neurodegeneration in 2006, primarily in association with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).[5] It was not until the late 2000s and early 2010s that researchers began to recognize a pattern of TDP-43 pathology that was distinct from ALS and FTLD in elderly individuals, often co-existing with but distinct from Alzheimer's disease pathology.[56][57]

A milestone in the history of LATE was the publication of a consensus report in 2019 by an international group of experts.[1] This report formally recognized LATE as a distinct disease entity, described its neuropathological criteria, and established its clinical relevance. This consensus was crucial for distinguishing LATE from other memory disorders of aging, and from other TDP-43 proteinopathies,[58] as required for raising awareness among clinicians and researchers.  There has been some debate and discussion as to optimal nomenclature for this condition. [59][60]

Initially, many cases of LATE were (and still are) diagnosed as Alzheimer's disease due to overlapping symptoms,[61] such as memory loss. As research has progressed, it became clear that LATE often (1:10 lifetime risk) occurred in the absence of significant Alzheimer's pathology,[3] prompting a re-evaluation of past cases that were presumed to have Alzheimer's disease. Research then began to unravel the unique pathophysiological mechanisms of LATE, and how TDP-43 abnormalities contribute to neurodegeneration.[10] The recognition that TDP-43 pathology follows a predictable pattern within the brain helped refine diagnostic and staging criteria. Researchers have also focused on understanding how aging influences TDP-43 pathology, with LATE providing a model for studying age-related cellular and molecular changes in the brain.

Society and culture

[edit]

The frequent presence of LATE in dementia of aging that has a different underlying mechanism from Alzheimer's disease has important implications for research and for patients, families, and healthcare systems. LATE leads to progressive cognitive decline, primarily affecting memory and other cognitive functions critical for daily activities and independence. As the clinical syndrome of dementia advances, patients may experience difficulties in communication, decision-making, and maintaining relationships.[62] The cognitive decline associated with LATE can lead to feelings of frustration, confusion, and depression in patients and caregivers.[63][64] Coping with the loss of cognitive abilities and the awareness of declining health can significantly impact emotional well-being in patients and families, and dementia also has a very large economic impact.[63][65]

Stigma surrounding dementia and cognitive decline may lead to social isolation and discrimination against individuals with LATE (as well as other dementia-related illnesses), and their families.[66][67] Cultural attitudes towards aging and cognitive impairment can influence how LATE is perceived and addressed within communities.[68] Advocacy organizations and community initiatives play a vital role in raising awareness about LATE (and other Alzheimer's-related dementia disorders), reducing stigma, and advocating for better support and resources for patients and caregivers.[63]

References

[edit]
  1. ^ a b c d e f g h i j Nelson, PT; Dickson, DW; Trojanowski, JQ; Jack, CR; Boyle, PA; Arfanakis, K; et al. (June 2019). "Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report". Brain: A Journal of Neurology. 142 (6): 1503–27. doi:10.1093/brain/awz099. ISSN 1460-2156. PMC 6536849. PMID 31039256.
  2. ^ a b Montine, TJ; Phelps, C H; Beach, TG; Bigio, EH; Cairns, NJ; Dickson, DW; et al. (January 2012). "National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach". Acta Neuropathologica. 123 (1): 1–11. doi:10.1007/s00401-011-0910-3. ISSN 1432-0533. PMC 3268003. PMID 22101365.
  3. ^ a b c d e Nelson, Peter T.; Brayne, Carol; Flanagan, Margaret E.; et al. (July 2022). "Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts". Acta Neuropathologica. 144 (1): 27–44. doi:10.1007/s00401-022-02444-1. ISSN 1432-0533. PMC 9552938. PMID 35697880.
  4. ^ Lee, Edward B.; Porta, Sílvia; Michael Baer, G.; Xu, Yan; Suh, EunRan; Kwong, Linda K.; Elman, Lauren; Grossman, Murray; Lee, Virginia M.-Y.; Irwin, David J.; Van Deerlin, Vivianna M.; Trojanowski, John Q. (2017-01-27). "Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration". Acta Neuropathologica. 134 (1): 65–78. doi:10.1007/s00401-017-1679-9. ISSN 1432-0533. PMC 5521959. PMID 28130640.
  5. ^ a b Neumann, Manuela; Sampathu, Deepak M.; Kwong, Linda K.; et al. (2006-10-06). "Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis". Science (New York, N.Y.). 314 (5796): 130–133. doi:10.1126/science.1134108. ISSN 1095-9203. PMID 17023659.
  6. ^ a b Josephs, K. A.; Whitwell, J. L.; Knopman, D. S.; et al. (2008-05-06). "Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype". Neurology. 70 (19 Pt 2): 1850–1857. doi:10.1212/01.wnl.0000304041.09418.b1. ISSN 1526-632X. PMC 2779031. PMID 18401022.
  7. ^ Hu, William T.; Josephs, Keith A.; Knopman, David S.; et al. (August 2008). "Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease". Acta Neuropathologica. 116 (2): 215–220. doi:10.1007/s00401-008-0400-4. ISSN 0001-6322. PMC 3404722. PMID 18592255.
  8. ^ a b c Nelson, Peter T.; Fardo, David W.; Wu, Xian; et al. (2024-05-22). "Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis". Journal of Neuropathology and Experimental Neurology. 83 (6): 396–415. doi:10.1093/jnen/nlae032. ISSN 1554-6578. PMC 11110076. PMID 38613823.{{cite journal}}: CS1 maint: PMC format (link)
  9. ^ Young, Alexandra L.; Vogel, Jacob W.; Robinson, John L.; et al. (2023-07-03). "Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies". Brain: A Journal of Neurology. 146 (7): 2975–2988. doi:10.1093/brain/awad145. ISSN 1460-2156. PMC 10317181. PMID 37150879.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ a b c Nag, Sukriti; Schneider, Julie A. (September 2023). "Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases". Nature Reviews. Neurology. 19 (9): 525–541. doi:10.1038/s41582-023-00846-7. ISSN 1759-4766. PMC 10964248. PMID 37563264.{{cite journal}}: CS1 maint: PMC format (link)
  11. ^ a b Duong, Michael Tran; Wolk, David A. (November 2022). "Limbic-Predominant Age-Related TDP-43 Encephalopathy: LATE-Breaking Updates in Clinicopathologic Features and Biomarkers". Current Neurology and Neuroscience Reports. 22 (11): 689–698. doi:10.1007/s11910-022-01232-4. ISSN 1534-6293. PMC 9633415. PMID 36190653.
  12. ^ a b c Kapasi, Alifiya; Yu, Lei; Boyle, Patricia A.; et al. (2020-10-06). "Limbic-predominant age-related TDP-43 encephalopathy, ADNC pathology, and cognitive decline in aging". Neurology. 95 (14): e1951–e1962. doi:10.1212/WNL.0000000000010454. ISSN 1526-632X. PMC 7682843. PMID 32753441.
  13. ^ Mesulam, M. M. (1985-05-03). "Dementia: its definition, differential diagnosis, and subtypes". JAMA. 253 (17): 2559–2561. ISSN 0098-7484. PMID 3981786.
  14. ^ Hamilton, Calum A.; Matthews, Fiona E.; Attems, Johannes; Donaghy, Paul C.; Erskine, Daniel; Taylor, John-Paul; Thomas, Alan J. (June 2024). "Associations between multimorbidity and neuropathology in dementia: consideration of functional cognitive disorders, psychiatric illness and dementia mimics". The British Journal of Psychiatry: The Journal of Mental Science. 224 (6): 237–244. doi:10.1192/bjp.2024.25. ISSN 1472-1465. PMC 7615979. PMID 38584319.
  15. ^ Nelson, Ruth S.; Abner, Erin L.; Jicha, Gregory A.; et al. (2023-06-02). "Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort". Acta Neuropathologica Communications. 11 (1): 89. doi:10.1186/s40478-023-01576-z. ISSN 2051-5960. PMC 10236713. PMID 37269007.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  16. ^ Katsumata, Yuriko; Fardo, David W.; Shade, Lincoln M. P.; et al. (2023-08-21). "LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry". Journal of Neuropathology and Experimental Neurology. 82 (9): 760–768. doi:10.1093/jnen/nlad059. ISSN 1554-6578. PMC 10440720. PMID 37528055.{{cite journal}}: CS1 maint: PMC format (link)
  17. ^ Dugan, Adam J.; Nelson, Peter T.; Katsumata, Yuriko; et al. (2021-09-15). "Analysis of genes (TMEM106B, GRN, ABCC9, KCNMB2, and APOE) implicated in risk for LATE-NC and hippocampal sclerosis provides pathogenetic insights: a retrospective genetic association study". Acta Neuropathologica Communications. 9 (1): 152. doi:10.1186/s40478-021-01250-2. ISSN 2051-5960. PMC 8442328. PMID 34526147.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ^ Yu, Lei; De Jager, Philip L.; Yang, Jingyun; et al. (2015-03-03). "The TMEM106B locus and TDP-43 pathology in older persons without FTLD". Neurology. 84 (9): 927–934. doi:10.1212/WNL.0000000000001313. ISSN 1526-632X. PMC 4351662. PMID 25653292.
  19. ^ Murray, Melissa E.; Cannon, Ashley; Graff-Radford, Neill R.; et al. (September 2014). "Differential clinicopathologic and genetic features of late-onset amnestic dementias". Acta Neuropathologica. 128 (3): 411–421. doi:10.1007/s00401-014-1302-2. ISSN 1432-0533. PMC 4412022. PMID 24899141.
  20. ^ Dickson, Dennis W.; Baker, Matthew; Rademakers, Rosa (2010). "Common variant in GRN is a genetic risk factor for hippocampal sclerosis in the elderly". Neuro-Degenerative Diseases. 7 (1–3): 170–174. doi:10.1159/000289231. ISSN 1660-2862. PMC 2859236. PMID 20197700.
  21. ^ Nelson, Peter T.; Estus, Steven; Abner, Erin L.; et al. (2014). "ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology". Acta Neuropathologica. 127 (6): 825–843. doi:10.1007/s00401-014-1282-2. ISSN 1432-0533. PMC 4113197. PMID 24770881.
  22. ^ a b Yang, Hyun-Sik; White, Charles C.; Klein, Hans-Ulrich; et al. (2020-08-05). "Genetics of Gene Expression in the Aging Human Brain Reveal TDP-43 Proteinopathy Pathophysiology". Neuron. 107 (3): 496–508.e6. doi:10.1016/j.neuron.2020.05.010. ISSN 1097-4199. PMC 7416464. PMID 32526197.
  23. ^ Dugan, Adam J.; Nelson, Peter T.; Katsumata, Yuriko; et al. (March 2022). "Association between WWOX/MAF variants and dementia-related neuropathologic endophenotypes". Neurobiology of Aging. 111: 95–106. doi:10.1016/j.neurobiolaging.2021.10.011. ISSN 1558-1497. PMC 8761217. PMID 34852950.
  24. ^ a b Carlos, Arenn F.; Tosakulwong, Nirubol; Weigand, Stephen D.; et al. (July 2022). "Frequency and distribution of TAR DNA-binding protein 43 (TDP-43) pathology increase linearly with age in a large cohort of older adults with and without dementia". Acta Neuropathologica. 144 (1): 159–160. doi:10.1007/s00401-022-02434-3. ISSN 1432-0533. PMC 9943023. PMID 35536384.
  25. ^ Neumann, Manuela; Perneel, Jolien; Cheung, Simon; et al. (July 2023). "Limbic-predominant age-related TDP-43 proteinopathy (LATE-NC) is associated with abundant TMEM106B pathology". Acta Neuropathologica. 146 (1): 163–166. doi:10.1007/s00401-023-02580-2. ISSN 1432-0533. PMID 37171635.
  26. ^ Nicks, Raymond; Clement, Nathan F.; Alvarez, Victor E.; et al. (April 2023). "Repetitive head impacts and chronic traumatic encephalopathy are associated with TDP-43 inclusions and hippocampal sclerosis". Acta Neuropathologica. 145 (4): 395–408. doi:10.1007/s00401-023-02539-3. ISSN 1432-0533. PMID 36681782.
  27. ^ GBD 2021 Risk Factors Collaborators (2024-05-18). "Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021". Lancet (London, England). 403 (10440): 2162–2203. doi:10.1016/S0140-6736(24)00933-4. ISSN 1474-547X. PMC 11120204. PMID 38762324.{{cite journal}}: CS1 maint: PMC format (link)
  28. ^ Kapasi, Alifiya; Yu, Lei; Leurgans, Sue E.; et al. (May 2024). "Association between hippocampal microglia, AD and LATE-NC, and cognitive decline in older adults". Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 20 (5): 3193–3202. doi:10.1002/alz.13780. ISSN 1552-5279. PMC 11095444. PMID 38494787.{{cite journal}}: CS1 maint: PMC format (link)
  29. ^ a b Cheng, Flora; Chapman, Tyler; Zhang, Selina; et al. (April 2024). "Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease". Ageing Research Reviews. 96: 102246. doi:10.1016/j.arr.2024.102246. ISSN 1872-9649. PMID 38401571.
  30. ^ Cohen, Todd J.; Lee, Virginia M. Y.; Trojanowski, John Q. (November 2011). "TDP-43 functions and pathogenic mechanisms implicated in TDP-43 proteinopathies". Trends in Molecular Medicine. 17 (11): 659–667. doi:10.1016/j.molmed.2011.06.004. ISSN 1471-499X. PMC 3202652. PMID 21783422.
  31. ^ Nilaver, Benjamin I.; Urbanski, Henryk F. (2023). "Mechanisms underlying TDP-43 pathology and neurodegeneration: An updated Mini-Review". Frontiers in Aging Neuroscience. 15: 1142617. doi:10.3389/fnagi.2023.1142617. ISSN 1663-4365. PMC 10034072. PMID 36967829.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  32. ^ Amador-Ortiz, Catalina; Ahmed, Zeshan; Zehr, Cynthia; et al. (March 2007). "Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration". Acta Neuropathologica. 113 (3): 245–252. doi:10.1007/s00401-006-0183-4. ISSN 0001-6322. PMC 1794627. PMID 17195931.
  33. ^ Gauthreaux, Kathryn M.; Teylan, Merilee A.; Katsumata, Yuriko; et al. (2022-04-05). "Limbic-Predominant Age-Related TDP-43 Encephalopathy: Medical and Pathologic Factors Associated With Comorbid Hippocampal Sclerosis". Neurology. 98 (14): e1422–e1433. doi:10.1212/WNL.0000000000200001. ISSN 1526-632X. PMC 8992604. PMID 35121671.
  34. ^ Li, Janice X.; Nguyen, Hannah L.; Qian, Tianchen; et al. (2023). "Longitudinal hippocampal atrophy in hippocampal sclerosis of aging". Aging Brain. 4: 100092. doi:10.1016/j.nbas.2023.100092. ISSN 2589-9589. PMC 10448324. PMID 37635712.{{cite journal}}: CS1 maint: PMC format (link)
  35. ^ Nelson, Peter T.; Abner, Erin L.; Schmitt, Frederick A.; et al. (January 2010). "Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons". Brain Pathology (Zurich, Switzerland). 20 (1): 66–79. doi:10.1111/j.1750-3639.2008.00244.x. ISSN 1750-3639. PMC 2864342. PMID 19021630.
  36. ^ Neltner, Janna H.; Abner, Erin L.; Baker, Steven; et al. (January 2014). "Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing". Brain: A Journal of Neurology. 137 (Pt 1): 255–267. doi:10.1093/brain/awt318. ISSN 1460-2156. PMC 3891448. PMID 24271328.
  37. ^ Nelson, Peter T.; Schneider, Julie A.; Jicha, Gregory A.; et al. (August 2023). "When Alzheimer's is LATE: Why Does it Matter?". Annals of Neurology. 94 (2): 211–222. doi:10.1002/ana.26711. ISSN 1531-8249. PMC 10516307. PMID 37245084.{{cite journal}}: CS1 maint: PMC format (link)
  38. ^ Yu, Lei; Boyle, Patricia A.; Dawe, Robert J.; et al. (2020-01-14). "Contribution of TDP and hippocampal sclerosis to hippocampal volume loss in older-old persons". Neurology. 94 (2): e142–e152. doi:10.1212/WNL.0000000000008679. ISSN 1526-632X. PMC 6988988. PMID 31757868.
  39. ^ Makkinejad, Nazanin; Schneider, Julie A.; Yu, Junxiao; et al. (May 2019). "Associations of amygdala volume and shape with transactive response DNA-binding protein 43 (TDP-43) pathology in a community cohort of older adults". Neurobiology of Aging. 77: 104–111. doi:10.1016/j.neurobiolaging.2019.01.022. ISSN 1558-1497. PMC 6486844. PMID 30784812.
  40. ^ Zarow, Chris; Weiner, Michael W.; Ellis, William G.; et al. (July 2012). "Prevalence, laterality, and comorbidity of hippocampal sclerosis in an autopsy sample". Brain and Behavior. 2 (4): 435–442. doi:10.1002/brb3.66. ISSN 2162-3279. PMC 3432966. PMID 22950047.
  41. ^ Tazwar, Mahir; Evia, Arnold M.; Ridwan, Abdur Raquib; et al. (August 2024). "Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with abnormalities in white matter structural integrity and connectivity: An ex-vivo diffusion MRI and pathology investigation". Neurobiology of Aging. 140: 81–92. doi:10.1016/j.neurobiolaging.2024.04.002. ISSN 1558-1497. PMID 38744041.
  42. ^ Youssef, Hossam; Gatto, Rodolfo G.; Pham, Nha Trang Thu; et al. (2024). "TDP-43 Is Associated with Subiculum and Cornu Ammonis 1 Hippocampal Subfield Atrophy in Primary Age-Related Tauopathy". Journal of Alzheimer's disease: JAD. 99 (3): 1023–1032. doi:10.3233/JAD-240136. ISSN 1875-8908. PMID 38728190.
  43. ^ Jack, Clifford R.; Bennett, David A.; Blennow, Kaj; Carrillo, Maria C.; Feldman, Howard H.; Frisoni, Giovanni B.; Hampel, Harald; Jagust, William J.; Johnson, Keith A.; Knopman, David S.; Petersen, Ronald C.; Scheltens, Philip; Sperling, Reisa A.; Dubois, Bruno (2016-08-02). "A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers". Neurology. 87 (5): 539–547. doi:10.1212/WNL.0000000000002923. ISSN 1526-632X. PMC 4970664. PMID 27371494.
  44. ^ Huang, Shan; Wang, Yan-Jiang; Guo, Junhong (June 2022). "Biofluid Biomarkers of Alzheimer's Disease: Progress, Problems, and Perspectives". Neuroscience Bulletin. 38 (6): 677–691. doi:10.1007/s12264-022-00836-7. ISSN 1995-8218. PMC 9206048. PMID 35306613.
  45. ^ López-Carbonero, Juan I.; García-Toledo, Irene; Fernández-Hernández, Laura; Bascuñana, Pablo; Gil-Moreno, María J.; Matías-Guiu, Jordi A.; Corrochano, Silvia (2024-06-03). "In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use". Translational Neurodegeneration. 13 (1): 29. doi:10.1186/s40035-024-00419-8. ISSN 2047-9158. PMC 11149336. PMID 38831349.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  46. ^ Josephs, Keith A.; Murray, Melissa E.; Whitwell, Jennifer L.; et al. (April 2016). "Updated TDP-43 in Alzheimer's disease staging scheme". Acta Neuropathologica. 131 (4): 571–585. doi:10.1007/s00401-016-1537-1. ISSN 1432-0533. PMC 5946692. PMID 26810071.
  47. ^ Josephs, Keith A.; Murray, Melissa E.; Whitwell, Jennifer L.; et al. (March 2014). "Staging TDP-43 pathology in Alzheimer's disease". Acta Neuropathologica. 127 (3): 441–450. doi:10.1007/s00401-013-1211-9. ISSN 1432-0533. PMC 3944799. PMID 24240737.
  48. ^ Nag, Sukriti; Yu, Lei; Boyle, Patricia A.; et al. (2018-05-01). "TDP-43 pathology in anterior temporal pole cortex in aging and Alzheimer's disease". Acta Neuropathologica Communications. 6 (1): 33. doi:10.1186/s40478-018-0531-3. ISSN 2051-5960. PMC 5928580. PMID 29716643.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  49. ^ Nelson, Peter T.; Lee, Edward B.; Cykowski, Matthew D.; et al. (February 2023). "LATE-NC staging in routine neuropathologic diagnosis: an update". Acta Neuropathologica. 145 (2): 159–173. doi:10.1007/s00401-022-02524-2. ISSN 1432-0533. PMC 9849315. PMID 36512061.
  50. ^ a b Cite error: The named reference prognosis was invoked but never defined (see the help page).
  51. ^ Mikhailenko, Elizaveta; Colangelo, Kia; Tuimala, Jarno; Kero, Mia; Savola, Sara; Raunio, Anna; Kok, Eloise H.; Tanskanen, Maarit; Mäkelä, Mira; Puttonen, Henri; Mäyränpää, Mikko I.; Kumar, Darshan; Kaivola, Karri; Paetau, Anders; Tienari, Pentti J. (2024-06-28). "Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study". Brain: A Journal of Neurology: awae212. doi:10.1093/brain/awae212. ISSN 1460-2156. PMID 38938199.
  52. ^ Nelson, Peter T.; Head, Elizabeth; Schmitt, Frederick A.; et al. (May 2011). "Alzheimer's disease is not "brain aging": neuropathological, genetic, and epidemiological human studies". Acta Neuropathologica. 121 (5): 571–587. doi:10.1007/s00401-011-0826-y. ISSN 1432-0533. PMC 3179861. PMID 21516511.
  53. ^ Huie, Emily Z.; Escudero, Anthony; Saito, Naomi; Harvey, Danielle; Nguyen, My-Le; Lucot, Katherine L.; LaGrande, Jayne; Mungas, Dan; DeCarli, Charles; Lamar, Melissa; Schneider, Julie A.; Kapasi, Alifiya; Rissman, Robert A.; Teich, Andrew F.; Dugger, Brittany N. (2023). "TDP-43 Pathology in the Setting of Intermediate and High Alzheimer's Disease Neuropathologic Changes: A Preliminary Evaluation Across Ethnoracial Groups". Journal of Alzheimer's disease: JAD. 91 (4): 1291–1301. doi:10.3233/JAD-220558. ISSN 1875-8908. PMC 9974776. PMID 36617779.
  54. ^ Nag, Sukriti; Barnes, Lisa L.; Yu, Lei; et al. (2020-10-13). "Limbic-predominant age-related TDP-43 encephalopathy in Black and White decedents". Neurology. 95 (15): e2056–e2064. doi:10.1212/WNL.0000000000010602. ISSN 1526-632X. PMC 7713750. PMID 32759188.
  55. ^ Dickson, D. W.; Davies, P.; Bevona, C.; Van Hoeven, K. H.; Factor, S. M.; Grober, E.; Aronson, M. K.; Crystal, H. A. (1994). "Hippocampal sclerosis: a common pathological feature of dementia in very old (> or = 80 years of age) humans". Acta Neuropathologica. 88 (3): 212–221. doi:10.1007/BF00293396. ISSN 0001-6322. PMID 7810292.
  56. ^ Carlos, Arenn F.; Josephs, Keith A. (August 2022). "Frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43): its journey of more than 100 years". Journal of Neurology. 269 (8): 4030–4054. doi:10.1007/s00415-022-11073-3. ISSN 1432-1459. PMC 10184567. PMID 35320398.{{cite journal}}: CS1 maint: PMC format (link)
  57. ^ Wharton, Stephen B.; Simpson, Julie E.; Ince, Paul G.; et al. (August 2023). "Insights into the pathological basis of dementia from population-based neuropathology studies". Neuropathology and Applied Neurobiology. 49 (4): e12923. doi:10.1111/nan.12923. ISSN 1365-2990. PMC 10946587. PMID 37462105.{{cite journal}}: CS1 maint: PMC format (link)
  58. ^ de Boer, Eva Maria Johanna; Orie, Viyanti K.; Williams, Timothy; et al. (2020-11-11). "TDP-43 proteinopathies: a new wave of neurodegenerative diseases". Journal of Neurology, Neurosurgery, and Psychiatry. 92 (1): 86–95. doi:10.1136/jnnp-2020-322983. ISSN 1468-330X. PMC 7803890. PMID 33177049.
  59. ^ Josephs, Keith A.; Mackenzie, Ian; Frosch, Matthew P.; et al. (2019-09-01). "LATE to the PART-y". Brain: A Journal of Neurology. 142 (9): e47. doi:10.1093/brain/awz224. ISSN 1460-2156. PMC 6736234. PMID 31359030.
  60. ^ Nelson, Peter T.; Dickson, Dennis W.; Trojanowski, John Q.; et al. (2019-09-01). "Reply: LATE to the PART-y". Brain: A Journal of Neurology. 142 (9): e48. doi:10.1093/brain/awz226. ISSN 1460-2156. PMC 6931389. PMID 31359039.
  61. ^ Brenowitz, Willa D.; Monsell, Sarah E.; Schmitt, Frederick A.; et al. (2014). "Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both Alzheimer's disease and non-tauopathic frontotemporal lobar degeneration". Journal of Alzheimer's disease: JAD. 39 (3): 691–702. doi:10.3233/JAD-131880. ISSN 1875-8908. PMC 3946156. PMID 24270205.
  62. ^ Jenkins, Catharine; Feldman, Gerald (May 2018). "Recognition of preclinical signs of dementia: A qualitative study exploring the experiences of family carers and professional care assistants". Journal of Clinical Nursing. 27 (9–10): 1931–1940. doi:10.1111/jocn.14333. ISSN 1365-2702. PMID 29495091.
  63. ^ a b c "2024 Alzheimer's disease facts and figures". Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 20 (5): 3708–3821. May 2024. doi:10.1002/alz.13809. ISSN 1552-5279. PMC 11095490. PMID 38689398.{{cite journal}}: CS1 maint: PMC format (link)
  64. ^ Frederiksen, Kristian Steen; Lanctôt, Krista L.; Weidner, Wendy; Hahn-Pedersen, Julie Hviid; Mattke, Soeren (2023). "A Literature Review on the Burden of Alzheimer's Disease on Care Partners". Journal of Alzheimer's disease: JAD. 96 (3): 947–966. doi:10.3233/JAD-230487. ISSN 1875-8908. PMID 37980660.
  65. ^ Tay, Lyn Xuan; Ong, Siew Chin; Tay, Lynn Jia; et al. (March 2024). "Economic Burden of Alzheimer's Disease: A Systematic Review". Value in Health Regional Issues. 40: 1–12. doi:10.1016/j.vhri.2023.09.008. ISSN 2212-1102. PMID 37972428.
  66. ^ Petersen, Ronald C.; Weintraub, Sandra; Sabbagh, Marwan; et al. (2023-12-01). "A New Framework for Dementia Nomenclature". JAMA neurology. 80 (12): 1364–1370. doi:10.1001/jamaneurol.2023.3664. ISSN 2168-6157. PMID 37843871.
  67. ^ Bacsu, Juanita-Dawne; Kortzman, August; Fraser, Sarah; et al. (2023-04-11). "Understanding Intersectional Ageism and Stigma of Dementia: Protocol for a Scoping Review". JMIR research protocols. 12: e46093. doi:10.2196/46093. ISSN 1929-0748. PMC 10131922. PMID 37040178.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  68. ^ Poole, Marie; Tomkow, Louise; Tissa, Faith; Ogden, Margaret; Ngouala, Malcolm; Karagiannidou, Maria; Dixon, Josie; Damisa, Efioanwan; Hanratty, Barbara; Knapp, Martin; Dewhurst, Felicity (2024-06-20). "DECIDE (Diverse experiences of End-of-Life Care for Dementia) establishing consensus and capacity for future research through collaboration and co-production". The British Journal of General Practice: The Journal of the Royal College of General Practitioners. 74 (suppl 1): bjgp24X738153. doi:10.3399/bjgp24X738153. ISSN 1478-5242. PMID 38902092.

Further reading

[edit]


Retrieved from "https://en.wikipedia.org/w/index.php?title=User:WikiDan61/LATE&oldid=1233434540"