da Rocha JF, Lance ML, Luo R, Schlachter P, Moreira L, Iqbal MA, Kuhn P, Gardner RS, Valaris S, Islam MR, Gassner GM, Mazuera S, Healy K, Shastri S, Hibbert NB, Moran-Figueroa KV, Haley EB, Pfeiffer RD, Aygar S, Kastanenka KV, Brase L, Harari O, Benitez BA, Tucker NR, Wrann CD. Protective exercise responses in the dentate gyrus of Alzheimer's disease mouse model revealed with single-nucleus RNA-sequencing. Nat Neurosci. 2025 Jun 12; Epub 2025 Jun 12 PubMed.

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  1. In this exciting study, Joana da Rocha, Christiane Wrann, and colleagues, provide new information on how enhanced adult hippocampal neurogenesis (AHN) and exercise affect hippocampal function in Alzheimer’s disease. This study aligns with our previous work showing that enhancing AHN rescued learning and memory in FAD mice by restoring recruitment of immature neurons into the memory circuit and rescuing the transcription profile of the hippocampus (Mishra et al., 2022; Morrissey et al., 2025). 

    Particularly exciting is the new information on the neurovascular unit. Here, they identified a subpopulation of neurovascular-associated, CDH4high astrocytes that was scarce in AD and swelled with exercise. Cross information with human datasets showed that this population was increased in carriers of rs1582763-A, an intergenic allele associated with decreased risk for AD and high levels of sTREM2 in the cerebrovascular fluid. Little is known about the neurovascular unit in the hippocampus and of AHN specifically, and particularly in the context of AD. Additional studies should explore the neurovascular unit of AHN in health and AD.

    References:

    Mishra R, Phan T, Kumar P, Morrissey Z, Gupta M, Hollands C, Shetti A, Lopez KL, Maienschein-Cline M, Suh H, Hen R, Lazarov O. Augmenting neurogenesis rescues memory impairments in Alzheimer's disease by restoring the memory-storing neurons. J Exp Med. 2022 Sep 5;219(9) Epub 2022 Aug 19 PubMed.

    Morrissey ZD, Kumar P, Phan TX, Maienschein-Cline M, Leow A, Lazarov O. Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease. Front Dement. 2025;4:1546433. Epub 2025 Apr 16 PubMed.

    View all comments by Orly Lazarov

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