Neurotrophic factor-α1/carboxypeptidase E controls progression and reversal of Alzheimer's disease pathogenesis in mice.

ABSTRACT: Background: Neurotrophic Factor-α1/Carboxypeptidase E (NF-α1/CPE) is a pivotal neuroprotective protein implicated in rescuing cognitive decline associated with Alzheimer's disease (AD). However, its direct role in AD pathogenesis remains unexplored. Methods: We utilized the Cre/LoxP system to diminish NF-α1/CPE expression, and employed AAV-mediated overexpression of NF-α1/CPE. Results: NF-α1/CPE expression was significantly down-regulated in advanced stages of AD and with age in 5xFAD mice. Reduced NF-α1/CPE levels in the hippocampus of 5xFAD mice increased plaque burden, microglial cell count, disrupted synaptogenesis, and intensified cognitive impairments at 5 and 7 months. However, by 9 months, no further progression of detrimental effects was observed. Overexpressi

SUBMITTER: Fan FC 

PROVIDER: S-EPMC11840748 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature