Talk:Alzheimer's disease

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Featured article Alzheimer's disease is a featured article; it (or a previous version of it) has been identified as one of the best articles produced by the Wikipedia community. Even so, if you can update or improve it, please do so.
Main Page trophy This article appeared on Wikipedia's Main Page as Today's featured article on September 21, 2008.
          This article is of interest to the following WikiProjects:
WikiProject Medicine / Translation / Neurology / Psychiatry (Rated FA-class, Top-importance)
WikiProject icon This article is within the scope of WikiProject Medicine, which recommends that this article follow the Manual of Style for medicine-related articles and use high-quality medical sources. Please visit the project page for details or ask questions at Wikipedia talk:WikiProject Medicine.
Featured article FA  This article has been rated as FA-Class on the project's quality scale.
 Top  This article has been rated as Top-importance on the project's importance scale.
Taskforce icon
This article is supported by the Translation task force (marked as Top-importance).
Taskforce icon
This article is supported by the Neurology task force (marked as Top-importance).
Taskforce icon
This article is supported by the Psychiatry task force (marked as Mid-importance).
 
Note icon
Information from this article appears on Portal:Medicine in the Did you know section.
WikiProject Neuroscience (Rated FA-class, High-importance)
WikiProject icon This article is within the scope of WikiProject Neuroscience, a collaborative effort to improve the coverage of Neuroscience on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks.
Featured article FA  This article has been rated as FA-Class on the project's quality scale.
 High  This article has been rated as High-importance on the project's importance scale.
 
WikiProject Cognitive science (Rated FA-class, Mid-importance)
WikiProject icon This article is within the scope of WikiProject Cognitive science, a collaborative effort to improve the coverage of Cognitive science on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks.
Featured article FA  This article has been rated as FA-Class on the project's quality scale.
 Mid  This article has been rated as Mid-importance on the project's importance scale.
 
WikiProject Disability (Rated FA-class, High-importance)
WikiProject icon Alzheimer's disease is within the scope of WikiProject Disability. For more information, visit the project page, where you can join the project and/or contribute to the discussion.
Featured article FA  This article has been rated as FA-Class on the project's quality scale.
 High  This article has been rated as High-importance on the project's importance scale.
 
WikiProject Spoken Wikipedia
WikiProject icon This article is within the scope of WikiProject Spoken Wikipedia, a collaborative effort to improve the coverage of articles that are spoken on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks.
 
Wikipedia Version 1.0 Editorial Team / v0.5 / Vital
WikiProject icon This article has been reviewed by the Version 1.0 Editorial Team.
Taskforce icon
This article has been selected for Version 0.5 and subsequent release versions of Wikipedia.

Good summary article from New England Journal of Medicine (2004)[edit]

  • Cummings JL (2004 Jul). "Alzheimer's Disease". N Engl J Med 351 (1): 56–67. PMID 15229308. 

IGAP Result Missing from the Article's Genetics section[edit]

IGAP (The International Genomics of Alzheimer's Project {The largest GWAS study ever conducted in Alzheimer's disease}) is not mentioned in the article.

"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease". Nat Genet. 45 (12): 1452–1458. 2013 Dec. PMID 24162737. 

This result should be included in the genetics section. Jedit1 (talk) 23:11, 28 June 2014 (UTC)

The results should be included but mentioning the project itself is not really needed. What wording do you suggest? Doc James (talk · contribs · email) (if I write on your page reply on mine) 01:53, 29 June 2014 (UTC)

"A large GWAS study has found that the genes CASS4,CELF1,FERMT2,HLA-DRB5,INPP5D,MEF2C,NME8,PTK2B,SORL1,ZCWPW1,SlC24A4 also contribute to risk for Late Onset AD. Only CD33 did not replicate among the established AD genes."

The last 4 genes listed from recent GWAS ( i.e. ATP5H,EXOC4,CTNNA3, RNF219) in the wiki article are not widely accepted AD genes. These genes did not appear in the mega meta-analysis above, nor do they appear on Alzforum's Alzgene top 10. The Alzforum Alzgene top 10 list are the generally accepted list of AD genes. IGAP verified 9 of them.

A figure showing risk of AD versus frequency would be a great addition to the article. (I am not sure how to upload the file). Jedit1 (talk) 05:11, 29 June 2014 (UTC)

Okay updated. Doc James (talk · contribs · email) (if I write on your page reply on mine) 05:33, 29 June 2014 (UTC)

Apart from ApoE-ε4, IGAP considered CR1, BIN1, CD2AP, EPHA1, CLU, MS4A6A, PICALM, ABCA7,and CD33 to be known GWAS-defined genes for AD. However, CD33 did not replicate in the IGAP study.Jedit1 (talk) 15:17, 29 June 2014 (UTC)

I don't agree that anything from this study should be in WP - while it is a large study, it is still a primary source. here is the most recent review I could find; it discusses findings from GWAS discussed above. Let's use it instead, OK? Jytdog (talk) 15:29, 29 June 2014 (UTC)

The last edit removed the top 10 AD genes! The 10 established AD genes ( CR1,BIN1,...) should be re-added to the article! I am not sure about whether IGAP should be directly cited. The problem with the review articles is that they are only able to say IGAP says this, IGAP says that. None of the current studies have the massive scale that IGAP has. IGAP found 11 new AD genes and replicated the results in the meta-analysis!

I think it would be helpful to add an article in wiki about this new generation of mega GWAS. The genetics research community struggled (largely without success) for at least 20 years to decipher the genetics of illness. During the last year a new generation of massive GWAS has emerged that is revealing an impressive amount of the genetics of complex illnesses. IGAP is one such study. There is also a large psychiatric GWAS study underway for example, in schizophrenia http://www.med.unc.edu/cpg/news/banbury-presentation ). Look at page 21 for the exponential increase in number of SNPS that are expected to be found as GWAS size increases. There should be an article on wiki that documents this profound change in the ability of GWAS to unravel the complex architecture of many human diseases. Schizophrenia until recently was widely considered an undicipherable illness. However, the above url page 21, notes that GWAS studies of 100,000 to 200,000 people would unravel a substantial portion of the genetics of schizophrenia. If this idea were more broadly understood, then there might be political and social pressure exerted to move such GWAS forward, as there would be substantial rewards to finally solving these problems.

Perhaps we could incubate a page for mega GWAS on this talk page and then migrate the page to a wiki article. Jedit1 (talk) 18:55, 29 June 2014 (UTC)

The publication of IGAP is a primary source. Secondary sources are always preferred. And as I mentioned, there is at least one already that discusses IGAP. please see WP:MEDRS.
This appears to be a secondary source [1] Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:25, 30 June 2014 (UTC)
nope - two stages. first stage was new research from old data, and second stage was new research done based on the conclusions from first stage. primary source! big study for sure, but primary source.Jytdog (talk) 02:45, 30 June 2014 (UTC)
It was a "meta-analysis of genome-wide association studies" thus a secondary source. Doc James (talk · contribs · email) (if I write on your page reply on mine) 03:44, 30 June 2014 (UTC)

Text in question[edit]

More recent genome-wide association studies (GWAS) have found 19 areas in genes that appear to affect the risk.[1] These genes include: CASS4, CELF1, FERMT2, HLA-DRB5, INPP5D, MEF2C, NME8, PTK2B, SORL1, ZCWPW1, SlC24A4, CLU, PICALM, CR1, BIN1, MS4A, ABCA7, EPHA1, CD2AP,.[1]

Here is the text in question feel free to adjust above and I can add changes. Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:32, 30 June 2014 (UTC)

Apart from ApoE-ε4, IGAP considered CR1, BIN1, CD2AP, EPHA1, CLU, MS4A6A, PICALM, ABCA7,and CD33 to be known GWAS-defined genes for AD. However, CD33 did not replicate in the IGAP study.Jedit1 (talk) 15:17, 29 June 2014 (UTC)
The last edit removed the top 10 AD genes!!!!! The 10 established AD genes ( CR1,BIN1,...) should be re-added to the article! --Jedit1 (talk) 22:22, 30 June 2014 (UTC)

The article might also include reference to synergy in AD. For example, in this article Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease. J Med Genet. 41 (4). 2004 Apr. pp. 261–265. PMID 15060098.  all tricarriers (HFE C282Y, TF C2, APOE epsilon 4) developed AD OR=37.5, p<0.0001. Results replicated in 2 subsequent studies "Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease.". Am J Med Genet B Neuropsychiatr Genet. 153B (4): 955–959. 2010 June 5. PMID 20029940.  "Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project.". Neurobiol Aging. 33 (1): e1–13. 2012 Jan. PMID 20817350.  , though with lower ORs.

However, it is possible that the original results stand within the genetic and environemental context of the original study. Other recent studies have also found extreme AD geno-pheno risk sets (for example, "Risk factors for development of dementia in a unique six-year cohort study. I. An exploratory, pilot study of involvement of the E4 allele of apolipoprotein E, mutations of the hemochromatosis-HFE gene, type 2 diabetes, and stroke.". J Alzheimers Dis. 38 (4): 907–922. PMID 24081379.  Epsilon4 + diabetes, OR=13.5, epsilon4 + stroke, males OR=46.5).

These studies (especially the last) have profound implications for how our societies function. There must be areas in communities with extreme disability. Providing medical services that could reduce the synergistic (that is, multiplicative) increase that occurs from being tri or quad carriers of certain sets of genosets and/or phenosets would likely be a very wise (and cost effective) investment. It is especially relevant to note that the initial tricarriers noted above have a treatable illness (i.e iron overload). Furthermore, these cases of AD would truly be sporadic as such cases would likely not have a family history of AD. In the original study, over 6% of the AD patients had the rare triple combo. The articles noted that over 20% of Western European populations have various mutations in the HFE, TF etc. genes that increase risk of AD.--Jedit1 (talk) 22:22, 30 June 2014 (UTC)

Make a proposal regarding what you want the text changed to in the format:
I want to added "X" supported by ref Y. Doc James (talk · contribs · email) (if I write on your page reply on mine) 22:52, 30 June 2014 (UTC)

It might be better to create an Alzheimer genetics wiki page. Such a page might include a table similar to http://www.snpedia.com/index.php/Alzheimer%27s_disease,_late-onset_%28IGAP%29 . Providing the list of AD genes on the main AD page might not be that helpful. The table could show which mutations have large effect (e.g. APOE epsilon4 , which are rare (e.g. TREM2 p.R47H) etc.) . --Jedit1 (talk) 23:12, 30 June 2014 (UTC)

Sure. Please do. Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:02, 1 July 2014 (UTC)
Jedit1 & Doc James - I haven't read the GWAS cited above, so apologies if I am out of line, but shouldn't the added text say that GWAS "have found 19 areas in genes that appear to correlate to increased risk." rather than "... genes that appear to affect the risk."? Correlation does not equal causation, although the media would often have us believe otherwise. Biolprof (talk) 03:06, 18 July 2014 (UTC)
"appear to affect the risk" sort of means correlation but in simpler language. There is no claim of causation there. Doc James (talk · contribs · email) (if I write on your page reply on mine) 06:18, 18 July 2014 (UTC)

References[edit]

  1. ^ a b Lambert, JC (Dec 2013). "Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.". Nature genetics 45 (12): 1452–8. PMID 24162737. 

Please make new additions ABOVE this section to keep this section at the end of the talk page.

Semi-protected edit request on 4 June 2014[edit]

The following text should have "as" added to it. Specifically, it should read "such as the intake of metals".

"Some studies have shown an increased risk of developing AD with environmental factors such the intake of metals, particularly aluminium.[148] The quality of some of these studies has been criticised,[149]"

Since those sources were all quite dated (2008 and older), I went you one better and rewrote the para from a recent review on the (still hot) topic. LeadSongDog come howl! 16:49, 18 July 2014 (UTC)
Addressing the issue of aluminum intake is important as a great deal of alt med literature claims it as a cause but this is not supported by the evidence. Also merged with cause as it was not prevention. Doc James (talk · contribs · email) (if I write on your page reply on mine) 01:28, 19 July 2014 (UTC)

Possible source about smell and vision tests to detect Alzheimers[edit]

See here.--Tomwsulcer (talk) 10:36, 13 July 2014 (UTC)

Primary source around which a lot of hype was generated. We don't use things like this. Great analysis of this study and take-down of the hype around it here. Jytdog (talk) 11:44, 13 July 2014 (UTC)
NBC News and BBC are secondary sources, but in your view, you feel that they are unreliable for this story?--Tomwsulcer (talk) 12:29, 13 July 2014 (UTC) Okay, saw the guideline in MEDRS, I see what you mean. Yes, lots of back-and-forth in popular media, saying eat this, don't eat that, and then it changes ten years later; good idea to stick with medical journals.--Tomwsulcer (talk) 12:33, 13 July 2014 (UTC)
 :) Thanks! Jytdog (talk) 12:49, 13 July 2014 (UTC)

Cannabinoids for treatment of Alzheimer’s disease[edit]

This analysis (full text here) from March 2014 might be worth implementing into the main article. Thought I'd just leave this here for you experts who are more familiar with what should and should not go into the articles. — Preceding unsigned comment added by 76.27.36.219 (talk) 06:17, 27 July 2014 (UTC)