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Enhancing Adult Neurogenesis Rescues Hippocampal Cognitive Functions in an Alzheimer's Mouse Model

Lee, C.-C.; Calegari, F.

2026-03-25 neuroscience
10.64898/2026.03.25.713986 bioRxiv
Show abstract

Alzheimers disease (AD) is the most prevalent form of dementia, characterized by progressive memory loss, cognitive decline, and emotional dysregulation. Adult hippocampal neurogenesis (AHN) critically contributes to cognition and mood but undergoes precipitous decline during AD progression. Here, we investigated whether enhancing AHN through genetic expansion of endogenous neural stem cells (NSC) ameliorates AD-related phenotypes. Using lentiviral overexpression of the cell cycle regulators Cdk4 and CyclinD1 in the dentate gyrus of 3xTg-AD mouse, we show that enhancing AHN partially rescues hippocampal-specific cognitive functions, namely: spatial navigation and exploratory behavior. These findings show that endogenous NSC can be exploited to ameliorate hippocampal cognitive functions in AD, providing additional evidence for exploiting AHN as a promising therapeutic target for neurodegenerative disease.

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