| First Author | Masliah E | Year | 2001 |
| Journal | Proc Natl Acad Sci U S A | Volume | 98 |
| Issue | 21 | Pages | 12245-50 |
| PubMed ID | 11572944 | Mgi Jnum | J:72239 |
| Mgi Id | MGI:2152029 | Doi | 10.1073/pnas.211412398 |
| Citation | Masliah E, et al. (2001) beta -Amyloid peptides enhance alpha -synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc Natl Acad Sci U S A 98(21):12245-50 |
| abstractText | Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenetic pathways. We generated transgenic (tg) mice with neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The functional and morphological alterations in doubly tg mice resembled the Lewy-body variant of Alzheimer's disease. These mice had severe deficits in learning and memory, developed motor deficits before alpha-synuclein singly tg mice, and showed prominent age-dependent degeneration of cholinergic neurons and presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these inclusions were fibrillar in doubly tg mice, whereas all inclusions were amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted aggregation of alpha-synuclein in a cell-free system and intraneuronal accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may contribute to the development of Lewy-body diseases by promoting the aggregation of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal pathologies. Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated. |
