Talk:Alzheimer's disease research

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limit scope?
Question is whether to be broad, or to limit scope to DMDs only, for obvious reasons. Answer may effect final title.....io_editor (talk) 00:09, 24 March 2008 (UTC)
 * I think that for the moment it should be broad. A section could be syntomatic treatments under investigation, while other could be disease modyfying... If finally there is enough quality info the page could be splitted. However I believe that most editions would be on disease modyfing treatmentns.--Garrondo (talk) 15:03, 25 March 2008 (UTC)
 * Yes I think in time, if it has not happened already, the disease-modyfying info will overwhelm the less interesting symptomatic stuff....io_editor (talk) 16:34, 25 March 2008 (UTC)


 * I would like to see this article at least divided between research into the cause(s) of AD (we still don't even know if amyloid beta plaques and tau tangles are causes or symptoms), and research into treatments (the current primary focus of the article. Phantom in ca (talk) 20:45, 11 August 2013 (UTC)

MCI (Mild cognitive impairment)
I was going to expand a little on MCI treatment here, as there are a couple of promising drugs that are trying to catch A-Beta as far upstream as possible - but then I realise that the page is "AD". I really cannot see anyone being able to cover the vast range of the symptom drugs - of course such people exist, but they are few and the message is not very interesting (almost the opposite to the pathology research) - I doubt that it makes good thesis material today. My suggestion is again to change the title to focus on disease pathology - and to include MCI clinical development, as it has featured much the same themes (mice thru A-Beta, etc).io_editor (talk) 22:59, 28 March 2008 (UTC)

What is more - you can see the recent sub-section "improvements" (at least I think so!) - we will be very lucky to write even as much about the other hundred Phase III trials in AD symptoms, etc. Even if I had a lot of time, I could barely scratch the surface, and it would be extremely tedious.io_editor (talk) 23:03, 28 March 2008 (UTC)

Feel free to do it. --Garrondo (talk) 13:06, 29 March 2008 (UTC)

Surely MCI is part of AD and should be discussed here too. I find it disappointing that the discussion focuses on drugs rather than life style and other assessment techniques that could be helpful Imersion (talk) 15:02, 5 October 2018 (UTC)

History of article name changes

 * 23 March 2008 Garrondo created as Therapies under investigation for Alzheimer's disease
 * 29 March 2008‎ io io editor renamed to Clinical research to halt Alzheimer's disease & mild cognitve impairment (sic)
 * 1 April 2008 Orangemarlin renamed to Alzheimer's disease clinical research
 * 26 July 2013‎ DJ renamed to Alzheimer's disease research

Frustrating
io editor, you are becoming difficult to work with. You asked to put this table in the Alzheimer's article, and not only did you receive no consensus, the actual consensus was not to do it. So you create an article which might make sense, but instead you rename it (with a spelling error), put in what is essentially a giant advertisement for pharmaceuticals, create a huge mess, and continue along like we wouldn't notice. I wish there was a way you'd play nicer with the group. But you want to do your own thing. Orange Marlin Talk• Contributions 01:19, 30 March 2008 (UTC)
 * The consensus was in fact to do it here, and the discussion was that (per LeadSongDog, Chrispounds, Colin and io_editor) was to confine it to a narrrow range of notable/DMD, late-stage trials, which is exactly what this page is, despite it's broad name. No-one supported your notion then that ongoing clinical trials could be an "advertisement" for pharmaceuticals. I dont see a huge mess, I don't see any mess at all...io_editor (talk) 00:13, 2 April 2008 (UTC)
 * The title is anything but encyclopedic... It had much more sense the one before, and it does have a spelling error. I think it should be renamed as before. --Garrondo (talk) 10:14, 31 March 2008 (UTC)
 * I made above a "suggestion is again to change the title to focus on disease pathology" and you said feel free to do it. In the name I had chosen my use of "to" was in the sense of "toward" - which is Ok in technical language that I work in, but I agree, it is probably ambiguous at best for an encyclopedia...I will come back and perhaps pull the MCI therapies out - that needs some thought though, perhaps unnecessary.io_editor (talk) 00:13, 2 April 2008 (UTC)

Antihistamines
At this we have news of a new article in on Dimebon an old Russian antihistamine showing promising results in a Phase III trial. LeadSongDog (talk) 17:18, 18 July 2008 (UTC)
 * More complete cites:

More info on the Dimebon article.LeadSongDog (talk) 17:58, 18 July 2008 (UTC)

Methylene blue
The BBC is reporting that methylthioninium chloride, targetting Tau proteins, has been shown to "halt" decline in AD in a phase II trial with 321 subjects.
 * If it bears out, it is very exciting.LeadSongDog (talk) 22:55, 29 July 2008 (UTC)
 * If it bears out, it is very exciting.LeadSongDog (talk) 22:55, 29 July 2008 (UTC)
 * If it bears out, it is very exciting.LeadSongDog (talk) 22:55, 29 July 2008 (UTC)


 * Nothing directly corresponds at ClinicalTrials.gov.LeadSongDog (talk) 23:21, 29 July 2008 (UTC)
 * Based on a number of AP stories it would seem that methylthioninium chloride is simply one of many active ingredients. I've certainly heard of stranger things being used as inhibitors. In the mean time I've created a stub for 'rember' on the presumption that it's more than just a single compound.  I hate to have to source an article like this based solely on AP news stories, I'd much rather have a journal article to source, but if they've published on this study they've done it in such a way as to completely obscure their study from literature/database searches, or alternatively the publication is too new.--VectorPotential Talk 12:46, 30 July 2008 (UTC)
 * The papers at that conference don't hint at anything but MTC in their abstracts. They do refer to dosages of MTC in some of them.  I think we should wait for evidence before hinting at another active ingredient.LeadSongDog (talk) 17:41, 30 July 2008 (UTC)
 * So I'm assuming that methylthioninium chloride and methylene blue are the same thing? If that's the case, I believe that the generic chemical should be the article for rember.  That might be a WP:MEDMOS thing.   Orange Marlin  Talk• Contributions 19:39, 30 July 2008 (UTC)
 * The principal author has been on this topic for quite a while. See  and PubChem.LeadSongDog (talk) 22:03, 30 July 2008 (UTC)
 * Synonyms per this list from the NCI.LeadSongDog (talk) 22:49, 30 July 2008 (UTC)

Exclude trials?
At this edit a table of clinical trials was removed, with an edit comment saying that we don't link to clinical trials. That leaves us with at least two questions to answer. Where was that decision taken? What else would belong in an article about X disease clinical research if we don't link to the research? Or is the point simply that we don't link to primary sources per wp:MEDRS? If it is the latter, it reflects a misunderstanding of MEDRS. Simply asserting that a trial is being conducted is not a medical claim and does not absolutely require secondary sourcing. LeadSongDog come howl!  17:09, 17 January 2012 (UTC)
 * I completely agree with you and I put the table back in - also because you never got an answer to your questions.  Lova Falk     talk   10:06, 17 October 2012 (UTC)


 * I agree its fine to mention trials but if we have a table/list we should be clear on the criteria - Is it every phase III trial that has started ? Is there some commitment to keep the table up to date ? At the moment it says it is of ongoing trials but they all seem to have completed years ago. What criteria would make a worthwhile table ? Even phase III trials for AD might find too many to put in this article. - Rod57 (talk) 20:10, 13 March 2016 (UTC)


 * Current trials may be considered "original research ". Since many have failed before phase II and there is often times little data collected from phase III. It is important to keep trial data up to date and not include fresh, novel trials because they may not include enough facts. -Chembelle17 (talk) 23:49, 16 September 2016 (UTC)

Anecdotal treatments?
These are "clinical" just not widely reproduced.

There's a link between diabetes and Alzheimers. See 18952836 for details.

There is a "glucose starvation" theory of Alzheimer damage. A medical proponent, Dr. Mary Newport, wrote the book [ http://www.amazon.com/Alzheimers-Disease-What-There-Cure/dp/1591202930 ]"Alzheimer's Disease: What if there was a cure? The story of Ketones." She recounts anecdotal evidence of her husband's recovery after being dosed with coconut oil, a strong natural source of ketones, an alternative metabolic fuel that crosses the blood-brain barrier. There is an on-line summary at and a video at  Ray Van De Walker 14:38, 8 September 2012 (UTC)


 * I think we should mention them somewhere - but maybe in the main article rather than here ? - Rod57 (talk) 20:39, 13 March 2016 (UTC)

Heads up (News re Targeting the Unfolded Protein Response)
There's quite a buzz currently being generated by "Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice" Sci Transl Med 9 October 2013: Vol. 5, Issue 206, p. 206ra138, which reported on positive mouse trials of a drug to inhibit PERK (protein kinase RNA–like endoplasmic reticulum kinase). It's been the subject of a couple of BBC News items and others. We do not yet have a wp:MEDRS source that assesses it, though the news items do have quotes from some prominent specialists. LeadSongDog come howl!  22:16, 7 November 2013 (UTC)
 * But they always do. As I said on the main article talk page, I'm not yet convinced we need to cover this.  Sandy Georgia  (Talk) 14:19, 8 November 2013 (UTC)
 * Probably correct, but if there is any place for such coverage, it's here, not the main article. Frankly, it looks to me more like a promising investigatory hint for a different research thrust than an actual drug candidate. Even in mice the side effects are too serious. LeadSongDog come howl!  18:07, 8 November 2013 (UTC)
 * Some transient initial scholarly coverage in: Holt CE, Schuman EM. "The Central Dogma Decentralized: New Perspectives on RNA Function and Local Translation in Neurons" Neuron 30;80(3):648-57
 * Key bit: "Indeed, the first “effective” oral drug treatment that prevents neurodegeneration in a prion disease/Alzheimer’s mouse model targets a kinase (PERK) that shuts down protein synthesis as part of the unfolded protein response (Moreno et al., 2013)."


 * It's the very last thing the authors write prior to their conclusions, but the poison quotes on "effective" rather diminish the implicit emphasis. I'd keep waiting for something more. LeadSongDog come howl!  17:11, 13 November 2013 (UTC)

New review re Combotherapy and current concepts and future strategies for AD

 * There's an interesting review at which concludes "AD is not a one-gene, one-protein disease and should be attributed to a network of interactions between genes, proteins, organelles, cells, neurotransmitters, and the environment. Those disease-modifying agents currently being developed typically target one hypothesis and one protein. Thus, it is clear that a single drug for the successful treatment of AD is not yet available. It is reasonable to explore multi-target strategies and combination therapies. Based on RCTs and meta-analyses, the combination of ChEI and NMDA antagonists is well tolerated and safe, and may benefit patients with moderate-to-severe AD dementia. In addition, different disease-modifying agents targeting different pathogenic pathways could be used together, for example, monoclonal antibody targeting Aβ combined with substance-inhibiting tau aggregation or BACEI added with mitochondrial protectors. A better chance of fighting against this relentless disease would then be possible."LeadSongDog  come howl!  00:09, 24 October 2014 (UTC)

Suggestions to restructure article
If we keep the current name 'Alzheimer's disease research' perhaps have :
 * Intro eg highlighting Active areas of research
 * and the causal theories behind most treatment trials
 * organised with those with the most supporting evidence first (eg clinical, then in-vivo, then in-vitro, then speculation) ?


 * Research into the causes and disease process
 * animal models of AD
 * Research on earlier diagnosis
 * Research on treatments
 * therapy/target types (for different theories of causation)
 * specific drugs
 * notable trials with results
 * notable active late-stage trials
 * History (of theories/approaches that did not work) ? - Rod57 (talk) 19:27, 13 March 2016 (UTC)
 * Agree completely.If you are going to keep this title, you have to deal with more than just treatments: Diagnostic Tests; Models; Prevention; Clinical Trials.  Imersion (talk) 12:31, 11 December 2018 (UTC)

Why the section/table on Disease-modifying drug candidates
Disease-modifying (DM) is normally used in the context of rheumatoid arthritis treatments. Could be worth clarifying which mechanisms/targets are considered DM and which are not. - Rod57 (talk) 21:20, 13 March 2016 (UTC)

Also the table is described as of ongoing trials - but they have all completed - Is there any value in keeping the table (other than as a historical snapshot) ? - Rod57 (talk) 20:02, 13 March 2016 (UTC)
 * It's a common problem, (as seen at Clinicaltrials.gov). Trials without positive results often omit publishing, particularly when their research funding dries up. Good business does not always lead to good science. Then we are left with no citable source to say the trial has completed, or what it found. We could cite that database for a scheduled completion date and allow the readers to draw their own conclusions. To date, though, we still have no successful d-m drug candidates, though there have been several symptom-modifying ones. LeadSongDog come howl!  17:05, 17 May 2016 (UTC)

Update and/or change table in Disease-modifying drug candidates

 * The Comments text wraps too much, need wider column, may as well drop the Planned enrolment column ? and others ? Or drop the table format and make it into bullet lists ?
 * Is it worth deleting some rows or adding new rows ? What is the criteria to use ? Should say at top of table.
 * The table is outside the in clinical development section so are we to assume this a record of drugs whose development has been abandoned ?
 * It seems way out of date, and probably incomplete. - Rod57 (talk) 14:01, 2 March 2017 (UTC)

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tau as biomarker
Is this the article to mention Alzheimer’s Progression Predicted by Tau Protein, Not Amyloid in ? (Neither Alzheimer's disease nor tau protein seem appropriate.) - Rod57 (talk) 12:10, 17 May 2016 (UTC)
 * It's brand new primary research, so, not yet. Once it gets picked up by secondary sources, there may be more to work with.LeadSongDog come howl!  16:57, 17 May 2016 (UTC).

Immunotherapy seems the most promising treatment. Not analyzed here!
Immunotherapy and immunomodulatory therapy for AD seems very promising, but on this article it is referred briefly! The recent therapies have limiting effects and do not treat the disease. Reference: 84.205.241.2 (talk) 19:34, 5 September 2016 (UTC)
 * http://www.nature.com/news/alzheimer-s-treatment-appears-to-alleviate-memory-loss-in-small-trial-1.20509
 * https://www.sciencedaily.com/releases/2015/11/151105092219.htm\
 * http://www.neurodegenerationresearch.eu/2016/02/alzheimers-disease-a-new-immunotherapy-approach/


 * Indeed. Also the research on aducanumab is not mentioned so far. --Chris Howard (talk) 11:36, 24 September 2016 (UTC)
 * really? there have been several Phase III failures - immunotherapy has been a complete failure to date.  see here and here and probably 10,000 sources on this. we don't hype early clinical trial results, ever, and especially not in a field where there is almost a 100% failure rate in Phase III trials. Jytdog (talk) 16:46, 24 September 2016 (UTC)
 * This is an article on research about the topic after all, not only on actual treatments. Results (both positive and negative) could very well be indicated in this article, provided the necessary explanations are given. It's not a question of contributing to a hype but rather of stating the known facts and putting it all in context. --Chris Howard (talk) 16:55, 2 October 2016 (UTC)
 * yes that is what this article is for. it is not for unrealistic hype per the OP.  it should describe the trends and specify the failures. Jytdog (talk) 21:43, 2 October 2016 (UTC)
 * Exactly. We agree 100% so far. An example of what I would find helpful to mention in this article: A 2015 review article states that Amyloid Related Imaging Abnormalities (ARIA) are "the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer's disease"  . Others write that the condition called ARIA "is characterised by leakage of fluid from the blood into the brain" . It would make sense to mention and explain such things in this article. --Chris Howard (talk) 15:35, 3 October 2016 (UTC)
 * Amyloid-related imaging abnormalities are mentioned in alzheimers disease but not (yet) in this article. - Rod57 (talk) 14:07, 2 March 2017 (UTC)

Ref
User:Miroslavpohanka the reference you are adding has no value; no content is generated from it. Please stop adding it. Thanks. Jytdog (talk) 08:05, 30 September 2016 (UTC)

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tacked on refs
moving these here - they were tacked on in the reference section

80. Allam AR, Siva PA, Hanuman T, Srinubabu G. (2008). Bioinformatic analysis of Alzheimer’s disease and type2 diabetes mellitus: a bioinformatics approach. J Proteomics Bioinform S1: S050-S054. 81. 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. (2009). Convergence of integrins and EGF receptor signaling via PI3K/Akt/FoxO pathway in early gene Egr-1 expression. J Cell Physiol. 218(2):294-303. 82. Dubois M, Lalonde R, Julien JP, Strazielle C. (2005). Mice with the deleted neurofilament of low-molecular-weight (Nefl) gene: 1. Effects on regional brain metabolism. J. Neurosci Res. 80: 741-750. 83. Forde JE, Dale TC. (2007). Glycogen synthase kinase 3: A key regulator of cellular fate. Cell Mol Life Sci. 64:1930-1944. 84. Heese K, Nagai Y, Sawada T. (2002). The 3’ untranslated region of the new rat synaptic vesicle protein 2B mRNA transcript inhibits translational efficiency. Brain Res Mol Brain Res. 104:127-131. 85. Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, Martin JJ, Butler IJ, Mancias P, Papsozomenos SCh, Terespolsky D, Potocki L, Brown CW, Shy M, Rita DA, Tourney I, Kremensky I, Lupski JR, Timmerman V. (2003). Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain. 126(3):590-597. 86. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. (2003). Epidermal growth factor receptor: mechanisms of activation and signaling. Exp Cell Res. 284(1):31-53. 87. Lus G, Nelis E, Jordanova A, Lofgren A, Cavallaro T, Ammendola A, Melone MA, Rizzuto N, Timmerman V, Cotrufo R, De Jonghe P. (2003). Charcot-Marie-Tooth disease with giant axons: a clinicopathological and genetic entity. Neurology. 61(7):988-990. 88. MacGibbon GA, Lawlor PA, Walton M, Sirimanne E, Faull RL, Synek B, Mee E, Connor B, Dragunow M. (1997). Expression of Fos, Jun, and Krox family proteins in Alzheimer’s disease. Exp Neurol. 147(2):316-332. 89. Ongwijitwat S, Wong-Riley MT. (2004). Functional analysis of the rat cytochrome c oxidase subunit 6A1 promoter in primary neurons. Gene 337:163-171. 90. Ravetti MG, Rosso OA, Berretta R, Moscato P. (2010). Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus’ gene expression profiles in Alzheimer’s disease. PLoS ONE. 5(4): 1-41. 91. Sanchez-Chavez G, Salceda R. (2000). Effect of streptozotocin-induced diabetes on activities of cholinesterases in the rat retina. IUBMB Life. 49:283-287. 92. Siavelis JC, MBourdakou MM, Athanasiadis EI, Spyrou GM, Nikita KS. (2016). Bioinformatics methods in drug repurposing for Alzheimer’s disease. Brief. Bioinform. 17(2):322-335. 93. Siddiqui S, Fang M, Ni B, Lu D, Martin B, Maudsley S. (2012). Central role of the EGF receptor in neurometabolic aging. Int J Endocrinol. 2012:39428. 94. Spires TL, Molnar Z, Kind PC, Cordery PM, Upton AL, Blakemore C, Hannan AJ. (2005). Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signaling. Cereb Cortex. 15(4):385-393. 95. Tiveci S, Akin A, Cakir T, Saybasili H, Ulgen K. (2005). Modeling of calcium dynamics in brain energy metabolism and Alzheimer’s disease. Comput Biol Chem. 29: 151-162. 96. Wang L, Chiang HC, Wu W, Liang B, Xie Z, Yao X, Ma W, Du S, Zhong Y. (2012). Epidermal growth factor receptor is a preferred target for treating Amyloid-β-induced memory loss. Proc Natl Acad Sci USA. 109(41):16743-16748. 97. Washizuka S. Iwamoto K, Kakiuchi C, Bundo M, Kato T. (2009). Expression of mitochondrial complex I subunit gene NDUFV2 in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia. Neurosci Res. 63: 199-204.}}

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Promising murine results
A new paper out on Tau intracellular antigen 1 reduction looks very promising as confirmation of a new tauopathy model and as a possible disease modification. LeadSongDog come howl!  18:17, 20 November 2017 (UTC)

Treatment candidate and reference to add to "Treatments in clinical development: passive immunotherapy"
To the "Treatments in clinical development: passive immunotherapy", second paragraph, perhaps add "The UB-311 vaccine candidate is designed to target the same amyloid epitope as the Biogen aducanumab infused antibody therapy while avoiding T-cell-mediated inflmmation and potentially providing a wide therapeutic window.

Also seems like the first paragraph should read: "does not invoke the immune system _to produce antibodies at high titer levels for an extended period_" to improve clarity.

-- — Preceding unsigned comment added by Mahamenacloud (talk • contribs) 20:07, 14 May 2018 (UTC)
 * Note - added tag to top of page and request edit tag here. Jytdog (talk) 20:43, 14 May 2018 (UTC)

Reply 20-MAY-2018
Based on the feedback I received from another editor, as this claim speaks to a drug's potential therapeutic window, I'm going to request that a secondary reference be provided (if available) before this change is approved. .   spintendo ⋅ ⋅ )  15:31, 20 May 2018 (UTC)

National Alzheimer's Project Act
I'm curious why you removed the link to the National Alzheimer's Project Act? (The policy page you cited lists a bunch of different reasons.) It seems to be the way the U.S. federal government is coordinating this research, so it seemed relevant to me. I'm open to mentioning it in the article instead of linking it, though it does seem that more information will be appearing on the site as planning efforts continue, so it may be more news-oriented than article text typically is. -- Beland (talk) 17:20, 13 June 2018 (UTC)
 * Hello . The Act is a plan begun last year, with no research results to highlight to date, as best as I can see. I'm interested but don't see it as informative at present. From an encyclopedic view, it doesn't seem to add useful information for the lay encyclopedia user. It might be worthy of a mention within the article content, but I don't see where among current content or what can be said useful at present. --Zefr (talk) 17:35, 13 June 2018 (UTC)

Emily Heacock Peer Review
1. What does the article (or section) do well?

- I really like the section on “Disease-modifying drug candidates”. It’s very informative and it breaks down the information in a way that’s easy to understand for the reader. The available options for research and treatment are also very comprehensively outlined in the article and many of my questions were able to be answered as a I kept reading on.

2. What changes would you suggest overall?

- It might be beneficial to the article overall if more information could be added to the “Bioinformatics approach” section. It an interesting continuation of the development of the article and I would love to be able to learn more about it.

3. What is the most important thing that the author could do to improve his/her contribution?

- One thing that could take the article to the next level would be adding some more external links when it comes to technical vocabulary, in order to help the reader fully understand the terms being used.

4. Did you learn anything from your classmate's work that could be applicable to your own?

- I loved how this article used a table as a section and how clearly it came across. This is something that I would like to try and incorporate into my own article going forward to make the information content more thorough.

Heacock.e (talk) 00:11, 30 October 2018 (UTC)

Grossly out of date
There's an annual systematic review of the development pipeline, now in its fourth iteration. It doesn't seem to have been used at all!

It appears as if none of the phase III candidates listed in the article are still in active trials, though perhaps there are some name-variation issues. LeadSongDog come howl!  18:33, 11 July 2019 (UTC)

I agree, someone with knowledge of the latest clinical trials, please update the table. Fpbear (talk) 19:20, 11 July 2019 (UTC)


 * Following this discussion the page was redirected to Alzheimer's disease. LeadSongDog come howl!  20:56, 2 March 2020 (UTC)