%0 Journal Article
%T Neurofibrillary tangle-bearing neurons have reduced risk of cell death in mice with Alzheimer's pathology.
%A Zwang TJ
%A Sastre ED
%A Wolf N
%A Ruiz-Uribe N
%A Woost B
%A Hoglund Z
%A Fan Z
%A Bailey J
%A Nfor L
%A Buée L
%A Nilsson KPR
%A Hyman BT
%A Bennett RE
%J Cell Rep
%V 43
%N 8
%D 2024 Aug 27
%M 39096489
暂无%R 10.1016/j.celrep.2024.114574
%X A prevailing hypothesis is that neurofibrillary tangles play a causal role in driving cognitive decline in Alzheimer's disease (AD) because tangles correlate anatomically with areas that undergo neuronal loss. We used two-photon longitudinal imaging to directly test this hypothesis and observed the fate of individual neurons in two mouse models. At any time point, neurons without tangles died at >3 times the rate as neurons with tangles. Additionally, prior to dying, they became >20% more distant from neighboring neurons across imaging sessions. Similar microstructural changes were evident in a population of non-tangle-bearing neurons in Alzheimer's donor tissues. Together, these data suggest that nonfibrillar tau puts neurons at high risk of death, and surprisingly, the presence of a tangle reduces this risk. Moreover, cortical microstructure changes appear to be a better predictor of imminent cell death than tangle status is and a promising tool for identifying dying neurons in Alzheimer's.