TAU, AMYLOID-BETA, AND ALPHA-SYNUCLEIN: THREE PARTNERS IN CRIME —OBSERVATIONS OF A NEUROPATHOLOGIST

Abstract

Data from in vitro studies, tg animal models and from human post mortem studies suggest that amyloid beta (Ab), tau and alpha-synuclein (a-syn) may promote the aggregation of each other. For example, Ab induces phosporylation of a-syn at Ser129 in vitro (Swirski M et al, Alzheimer's Res Ther 2014 6:77) and a-syn pathology influences the topographical distribution of tau (Walker L et al, Acta Neuropathol 129:729–48). Here, we quantitatively assessed Ab, tau and a-syn pathology in a large cohort of human post mortem brains to investigate possible correlations and identify areas where such correlations are most prevalent. Our study cohort consisted of 140 post mortem brains including Alzheimer's disease (AD), Lewy body disease (LBD) and controls. Sections were stained with antibodies against Ab (4G8), tau (AT8) and a-syn (Novocastra). Quantitative assessment was based on automated image analysis and performed in 15 brain regions, covering a variety of neocortical and limbic areas. In AD, controls and LDB significant (P<0.05) correlations were seen between Ab and tau loads, while no correlations were found between Ab and a-syn loads. In LBD cases tau loads significantly (P<0.01) correlated with a-syn loads in the entorhinal and cingulate cortex. Not surprisingly our data indicate an interaction between Ab and tau across all groups and further corroborates high AD pathology in LBD cases, where tau, but not Ab, seems to interact with a-syn to promote their aggregation. Further studies are warranted to understand the underlying mechanisms of these interactions and to clarify if tau triggers a-syn pathology in LBD.