Neurofibrillary tangle-bearing neurons have reduced risk of cell death in mice with Alzheimer's pathology.
Cell Rep
; 43(8): 114574, 2024 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-39096489
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 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Emaranhados Neurofibrilares
/
Morte Celular
/
Doença de Alzheimer
/
Neurônios
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article