| First Author | Zwang TJ | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 8 | Pages | 114574 |
| PubMed ID | 39096489 | Mgi Jnum | J:353285 |
| Mgi Id | MGI:7710794 | Doi | 10.1016/j.celrep.2024.114574 |
| Citation | Zwang TJ, et al. (2024) Neurofibrillary tangle-bearing neurons have reduced risk of cell death in mice with Alzheimer's pathology. Cell Rep 43(8):114574 |
| abstractText | 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. |
