View unanswered posts | View active topics It is currently Thu Aug 28, 2014 9:30 pm



Reply to topic  [ 2 posts ] 
 Up to 50% of AD cases exhibit Lewy bodies 
Author Message

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Up to 50% of AD cases exhibit Lewy bodies
This is very interesting research out of UC Irvine. It's a genetic study in a mouse model where the mice develop both DLB and AD pathologies. No chance of my understanding much of this paper but the abstract is quite understandable. As many of you know, DLB commonly co-occurs with Alzheimer's pathology. But, I didn't know that "up to 50% of AD cases exhibit...the aggregation of alpha-synuclein into Lewy bodies." The "most common subtype of AD" is the so-called "Lewy body variant of Alzheimer's."

The abstract also notes: "Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction" than in patients with pure AD. And: "Together, our data support the notion that Abeta, tau, and alpha-synuclein interact in vivo to promote the aggregation and accumulation of each other." It had been previously hypothesized that these proteins promote the accumulation of one another because "plaques, tangles, and LBs [Lewy bodies] do not develop in high enough individual frequently to explain their co-occurrence simply by statistical overlap."

One of the authors, Dr. Trojanowski, is one of this country's top neuropathologists. He works at UPenn. Dr. Trojanowski has previously published a paper on these cases of triple protein-opathies, increasingly identified postmortem.

Robin



Journal of Neuroscience. 2010 May 26;30(21):7281-9.

Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline.

Clinton LK, Blurton-Jones M, Myczek K, Trojanowski JQ, LaFerla FM.
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California.

Abstract
Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of beta-amyloid (Abeta) plaques and tau-laden neurofibrillary tangles.

Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of alpha-synuclein into Lewy bodies. Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction.

Thus, Abeta, tau, and alpha-synuclein may interact synergistically to promote the accumulation of each other.

In this study, we used a genetic approach to generate a model that exhibits the combined pathologies of AD and dementia with Lewy bodies (DLB). To achieve this goal, we introduced a mutant human alpha-synuclein transgene into 3xTg-AD mice. As occurs in human disease, transgenic mice that develop both DLB and AD pathologies (DLB-AD mice) exhibit accelerated cognitive decline associated with a dramatic enhancement of Abeta, tau, and alpha-synuclein pathologies.

Our findings also provide additional evidence that the accumulation of alpha-synuclein alone can significantly disrupt cognition.

Together, our data support the notion that Abeta, tau, and alpha-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction.

PubMed ID#: 20505094 (see pubmed.gov for this abstract)


Fri Jun 04, 2010 1:25 am
Profile

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Re: Up to 50% of AD cases exhibit Lewy bodies
This commentary from two leading Seattle-based dementia researchers is about the mouse model described back in June (see earlier post). These mice had both DLB and AD pathologies in their brains. This commentary is an explanation of the importance of this particular mouse model. Further, it's an explanation of the links between AD, PD, PDD, and DLB. I found the first few paragraphs understandable along with the last paragraph.

The commentary is currently available for free online at:
http://alzres.com/content/2/5/26
(Save this article now to your hard drive if you want it. I've found that just because things are available for free now doesn't mean they'll be available for free in the future.)

The commentary's citation (PubMed ID#: 20854651) and abstract follow.


Alzheimer's Research & Therapy 2010 Sep 17;2(5):26.

Commentary
From model system to clinical medicine: pathophysiologic links of common proteinopathies.

McMillan PJ, Leverenz JB.
Mental Illness Research Education and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle, WA.

Recent clinical evidence suggests that Alzheimer disease (AD), Parkinson disease (PD), and dementia with Lewy bodies (DLB), though distinct neurological disorders, have some common pathological features that may have an impact on the clinical characteristics of these diseases. However, the question of whether these disorders have a common pathophysiology remains. Clinton and colleagues recently reported a mouse model that exhibits the combined pathologies of AD, PD, and DLB, a finding that may shed some light on this issue. Using this mouse model, the authors demonstrate that the pathogenic proteins amyloid beta, tau, and alpha-synuclein interact synergistically to enhance the accumulation of one another and accelerate cognitive decline. These data indicate shared pathogenic mechanisms and suggest the possibility that therapeutic interventions successfully targeting one of these pathogenic proteins have implications for a number of related neurodegenerative disorders.


Wed Sep 22, 2010 11:27 pm
Profile
Display posts from previous:  Sort by  
Reply to topic   [ 2 posts ] 

You cannot post new topics in this forum
You cannot reply to topics in this forum
You cannot edit your posts in this forum
You cannot delete your posts in this forum
You cannot post attachments in this forum

Search for:
Jump to:  
Powered by phpBB © 2000, 2002, 2005, 2007 phpBB Group.
Designed by STSoftware for PTF.
Localized by MaĆ«l Soucaze © 2010 phpBB.fr