Synergistic Interactions between Aβ, Tau, and α-Synuclein: Acceleration of Neuropathology and Cognitive Decline
Year: 2010
Type: article
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.
Source: Journal of Neuroscience
Institutions: University of California, Irvine, University of Pennsylvania
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Awards: G12099775, TRANSGENIC MOUSE MODEL OF INCLUSION BODY MYOSITIS, The Role of Beta-Amyloid Assembly States in Tau Pathology and Cognitive Decline, Parkinson's Disease and Dementia, The Alzheimer's Disease Research Center at the University of California, Irvine, Learning and Memory Impairments in Transgenic AD Models, G9000106966, G9000168176, Training in the Neurobiology of Aging and Alzheimers Disease
OpenAlex ID: W1973166472