Peters, Finn, Salihoglu, Hazal, Pratsch, Kathrin, Herzog, Ettienne, Pigoni, Martina, Lichtenthaler, Stefan, Neumann, Ulf, Brose, Nils and Herms, Jochen (2019) Tau deletion reduces beta-amyloid deposition by alleviating plaque-associated axonal damage. The EMBO Journal. ISSN 0261-41891460-2075

Abstract

Amyloid-β (Aβ) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer’s disease. The prevalent ‘amyloid cascade hypothesis’ posits that Aβ aggregates trigger tau-related pathology. However, it remains controversial whether the connection between Aβ and tau is indeed unidirectional. We monitored the impact of tau deletion on the temporal progression of Aβ pathology by performing chronic in vivo two-photon microscopy in transgenic Alzheimer mice. Tau deletion did not postpone the onset of Aβ deposition but effectively ameliorated plaque-associated axonal pathology and slowed down Aβ deposition. Importantly, tau deletion alleviated the accumulation of BACE1 around plaques and interrupted the vicious pathogenic cycle of increased Aβ deposition. Hence, our results are potentially relevant to improve the efficacy of prospective BACE1 inhibition clinical trials.

Item Type:	Article
Date Deposited:	26 Nov 2019 00:45
Last Modified:	26 Nov 2019 00:45
URI:	https://oak.novartis.com/id/eprint/37666