Neurofibrillary tangle-bearing neurons have reduced risk of cell death in mice with Alzheimer's pathology.

ABSTRACT: 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 tang

SUBMITTER: Zwang TJ 

PROVIDER: S-EPMC11441076 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature