A beta Accelerates the Spatiotemporal Progression of Tau Pathology and Augments Tau Amyloidosis in an Alzheimer Mouse Model

作者：Hurtado David E; Molina Porcel Laura; Iba Michiyo; Aboagye Awo K; Paul Steven M; Trojanowski John Q; Lee Virginia M Y^*

来源：American Journal Of Pathology, 2010, 177(4): 1977-1988.

DOI：10.2353/ajpath.2010.100346

Senile plaques formed by beta-amyloid peptides (A beta) and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau, a microtubule-associated protein, are the hallmark lesions of Alzheimer's disease (AD) in addition to loss of neurons. While several transgenic (Tg) mouse models have recapitulated aspects of AD-like A beta and tau pathologies, a spatiotemporal mapping paradigm for progressive NFT accumulation Is urgently needed to stage disease progression in AD mouse models. Braak and co-workers developed an effective and widely used NET staging paradigm for human AD brains. The creation of a Braak-like spatiotemporal staging scheme for tau pathology in mouse models would facilitate mechanistic studies of AD-like tau pathology. Such a scheme would also enhance the reproducibility of preclinical AD therapeutic studies. Thus, we developed a novel murine model of A beta and tau pathologies and devised a spatiotemporal scheme to stage the emergence and accumulation of NFTs with advancing age. Notably, the development of NFTs followed a spatiotemporal Braak-like pattern similar to that observed in authentic AD. More significantly, the presence of All accelerated NET formation and enhanced tau amyloidosis; however, tau pathology did not have the same effect on A beta pathology. This novel NET staging scheme provides new insights into the mechanisms of tau pathobiology, and we speculate that this scheme will prove useful for other basic and translational studies of AD mouse models. (Am J Pathol 2010, 177:1977-1988; DOI: 10.2353/ajpath.2010.100346)

• 出版日期2010-10