Wikipedia:Peer review/Alzheimer's disease/archive1

Alzheimer's disease

"On November 3, 1906 Alois Alzheimer travelled to the university city of Tübingen, Germany to present an unusual case of dementia. Auguste D. would become known as the first documented case of Alzheimer’s disease." We have a good article in Wikipedia that with some editing might qualify to be the featured article on November 3 2006 to commemorate the 100th year of its first public documentation.

Some points to consider:

the article is long, what sections might be abridged?
is it in line structurally with other diseases? The Manual of style has a slightly different format
do we get too technical?
are the risk factors too numerous and poorly substatiated

There were treatment recommendations produced by the American Association of Geriatric Psychiatrists that we could reference more heavily for the risk factors. The press has said that their review is fairly balanced, even though payers are not in favor of some of the therapies. --Chrispounds 00:54, 21 September 2006 (UTC)[reply]

Overall it seems that the clinical sections got a lot more attention than the biochemistry-related sections. The clinical information is much more thoroughly referenced than the rest of the article, which is rather bare of citations - particularly the pathology section. There are also a few external jumps to PubMed pages that should be converted to references before a FAC. I'm going to focus on the biochem-related information because a) it's in need of the most work, and b) I'm much less familiar with the clinical angle.

The emphases in the pathology section strike me as a bit odd, or possibly out of date. There's no specific mention of AD as a protein misfolding disease, for example, or that amyloidogenesis is hypothesized as a common disease pathway among AD, PD, and others. The fact that Abeta is a proteolytic byproduct of APP isn't explicitly mentioned either, although both are mentioned separately.
First, I'd suggest either expanding the "neurochemistry" subsection or merging with "microscopy" to form a larger subsection titled something like "biochemical characteristics". Perhaps some of this really belongs in the amyloid beta article, but there's a large body of literature on Abeta's mechanism of cytotoxicity that gets very short shrift here compared to the tau-vs-Abeta dispute, which admittedly has a cute name but as far as I know the tau-initiator hypothesis is fading fast. The more relevant dispute for drug development seems to be whether it is mature aggregated fibrils or intermediate oligomers that mediate cytotoxicity, and whether formation of fibril is actually protective. It might be worth noting here that a lot of drug-development work has been done with the aim of destabilizing or inhibiting fibrillization and that the toxic-oligomer theory would imply that that is a poor choice of approach.
You don't mention the well-established fact of Abeta-induced calcium influx causing apoptosis in vitro. If you wanted to get into detail, you could also discuss the membrane-permeabilization hypothesis of oligomer toxicity.
(Minor question) I remember having read studies suggesting that smokers have lower rates of AD compared to age-matched nonsmokers, and that nicotine inhibits fibrillization. Any recent data on that?
You don't seem to talk about the (hypothesized) role of oxidative stress in AD.
Last I knew, the synuclein-Abeta connection had only been made in mouse models - is there more recent data on humans?
Your rates of incidence are largely uncited, and sound like figures from US data alone. I don't see any discussion of rates of incidence globally, or possible country-by-country variations. IIRC India has an unusually low incidence.
There is a statement "The American Association for Geriatric Psychiatry published a consensus statement on Alzheimer's treatment in 2006" - this isn't very useful to know unless you're also going to add information on what the statement said.
The "risk factors" list has two lonely footnotes on their own line on my screen - are they meant to apply to the whole list? For completeness, I'd include one footnote per factor, even if there's some redundancy, unless they all come from a single source.

Opabinia regalis 22:54, 23 September 2006 (UTC)[reply]

It seems like you have taken care of all of the issues you brought up--and in magnificent and well documented style. I am going to review the clinical side and add some more cross-references. Thanks for your contribution. It is getting long, but it presents all prominent sides of the disease mechanism. If we created another article (with your new content), say "Alzheimer's Disease Mechanism Debate" and then summarized things into a paragraph, it might be easier for the reader. --Chrispounds 14:25, 27 September 2006 (UTC)[reply]

I tried to cover the biochemistry - I would suggest more citations for the clinical features and diagnosis sections; especially if it goes to FAC, this will be a rather high-profile article on a subject that the public has a high interest in. I agree that the section I added is a bit long - I was initially thinking of forking it off to the individual pages on tau and Abeta, but I like your idea better. I think something like "Biochemistry of Alzheimer's disease" would be a clear title that allows room for expansion - emphasizing the debate in the title has the potential to get out of date if someone's research goes unusually well :) Opabinia regalis 01:13, 28 September 2006 (UTC)[reply]

Per WP:LAYOUT, External links should be last. Please include PMIDs on all of your journal studies (see cystic fibrosis). Notable patients should be referenced: refer to WP:MEDMOS and Sociological and cultural aspects of Tourette syndrome. Sandy 22:53, 30 September 2006 (UTC)[reply]

I will get to the PMID updates and will look at options for the notable patients. Do we want a section or just a link to the list? Thanks! --Chrispounds 04:25, 1 October 2006 (UTC)[reply]

The problem with the link to the list is that the list is completely unreferenced, so the reader is not given sources anywhere. The first known case might be mentioned in History, and Hayworth would also be worthy of mention in the main article, but all need to be sourced somewhere. We see the same problem at FACs for Universities, where Notable alumni aren't referenced: we can't ask Wiki readers to take our word for it. Sandy 16:30, 1 October 2006 (UTC)[reply]

There was a PBS series made from a book called The Foregetting that can be a great source for the public figures. I have a copy on order, but the website can be a source. The documentary won an Emmy in 2004. --Chrispounds 15:36, 2 October 2006 (UTC)[reply]

I had another look, since you're hard at work. The lead really needs to avoid definitions and medical jargon; that detail can be provided in the body. And, there are some broad swatches of text with no inline citations. Sandy 23:03, 1 October 2006 (UTC)[reply]

Please see automated peer review suggestions here. Thanks, Ruhrfisch 15:28, 14 October 2006 (UTC)[reply]