Inhibition of amyloid-? plaque formation by ?-synuclein
22.06.2015
Bachhuber T, Katzmarski N, McCarter JF, Loreth D, Tahirovic S, Kamp F, Abou-Ajram C, Nuscher B, Serrano-Pozo A, Mller A, Prinz M, Steiner H, Hyman BT, Haass C, Meyer-Luehmann M.
Nat Med. 2015 Jul;21(7):802-7.
Amyloid-b (Ab) plaques and a-synuclein (a-syn) rich Lewy bodies are the major neuropathological hallmarks of Alzheimer's (AD) and Parkinson's disease, respectively. An overlap of pathologies is found in most patients of Dementia with Lewy Bodies (DLB)1 and in more than 50 % of AD cases. Here, we performed intracerebral injections of a syn containing preparations into amyloid precursor protein (APP) transgenic mice. Unexpectedly, a-syn failed to cross-seed A? plaques in vivo, but rather inhibited plaque formation in APPPS1xa-synA30P mice. This was accompanied by increased A? levels in CSF despite unchanged overall A? levels. Notably, the seeding activity of A?- containing brain homogenates was significantly reduced by a syn, and Ab deposition was suppressed in grafted tissue from a-syn transgenic mice. Thus, we conclude that the interaction between A? and a-syn leads to crossinhibition of A? deposition and to reduced plaque formation.
