In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 30, No. 21 ( 2010-05-26), p. 7281-7289
Abstract:
Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of α-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, Aβ, tau, and α-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 α-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 Aβ, tau, and α-synuclein pathologies. Our findings also provide additional evidence that the accumulation of α-synuclein alone can significantly disrupt cognition. Together, our data support the notion that Aβ, tau, and α-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.0490-10.2010
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2010
detail.hit.zdb_id:
1475274-8
SSG:
12
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