Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Clinton, LK; Blurton-Jones, M; Myczek, K; Trojanowski, JQ; LaFerla, FM
Published Date
- May 26, 2010
Published In
Volume / Issue
- 30 / 21
Start / End Page
- 7281 - 7289
PubMed ID
- 20505094
Pubmed Central ID
- PMC3308018
Electronic International Standard Serial Number (EISSN)
- 1529-2401
Digital Object Identifier (DOI)
- 10.1523/JNEUROSCI.0490-10.2010
Language
- eng
Conference Location
- United States