Article Dans Une Revue Cell Reports Année : 2024

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

Résumé

A prevailing hypothesis is that neurofibrillary tangles play a causal role in driving cognitive decline in Alz- heimer’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 neu- rons 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 neu- rons 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.
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hal-04687045 , version 1 (04-09-2024)

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T. J. Zwang, E. D. Sastre, N. Wolf, N. Ruiz-Uribe, B. Woost, et al.. Neurofibrillary tangle-bearing neurons have reduced risk of cell death in mice with Alzheimer's pathology. Cell Reports, 2024, Cell Reports, 43 (8), pp.114574. ⟨10.1016/j.celrep.2024.114574⟩. ⟨hal-04687045⟩

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