| First Author | Bachhuber T | Year | 2015 |
| Journal | Nat Med | Volume | 21 |
| Issue | 7 | Pages | 802-7 |
| PubMed ID | 26099047 | Mgi Jnum | J:224864 |
| Mgi Id | MGI:5689219 | Doi | 10.1038/nm.3885 |
| Citation | Bachhuber T, et al. (2015) Inhibition of amyloid-beta plaque formation by alpha-synuclein. Nat Med 21(7):802-7 |
| abstractText | Amyloid-beta (Abeta) plaques and alpha-synuclein (alpha-syn)-rich Lewy bodies are the major neuropathological hallmarks of Alzheimer's disease (AD) and Parkinson's disease, respectively. An overlap of pathologies is found in most individuals with dementia with Lewy bodies (DLB) and in more than 50% of AD cases. Their brains display substantial alpha-syn accumulation not only in Lewy bodies, but also in dystrophic neurites decorating Abeta plaques. Several studies report binding and coaggregation of Abeta and alpha-syn, yet the precise role of alpha-syn in amyloid plaque formation remains elusive. Here we performed intracerebral injections of alpha-syn-containing preparations into amyloid precursor protein (APP) transgenic mice (expressing APP695(KM670/671NL) and PSEN1(L166P) under the control of the neuron-specific Thy-1 promoter; referred to here as 'APPPS1'). Unexpectedly, alpha-syn failed to cross-seed Abeta plaques in vivo, but rather it inhibited plaque formation in APPPS1 mice coexpressing SNCA(A30P) (referred to here as 'APPPS1 x [A30P]aSYN' double-transgenic mice). This was accompanied by increased Abeta levels in cerebrospinal fluid despite unchanged overall Abeta levels. Notably, the seeding activity of Abeta-containing brain homogenates was considerably reduced by alpha-syn, and Abeta deposition was suppressed in grafted tissue from [A30P]aSYN transgenic mice. Thus, we conclude that an interaction between Abeta and alpha-syn leads to inhibition of Abeta deposition and to reduced plaque formation. |
