02679nas a2200349   4500000000100000000000100001008004100002260001500043653002300058653002400081100001800105700002000123700001800143700002300161700002500184700002100209700001300230700001200243700001800255700002100273700001600294700002200310700001800332700002700350700001800377700001700395245008200412856005500494300000900549520175700558022001402315       2026                            d  c2026-02-2510aAdult neurogenesis10aAlzheimer's disease1 aAhmed Disouky1 aMark A. Sanborn1 aK. R. Sabitha1 aMostafa M. Mostafa1 aIvan Alejandro Ayala1 aDavid A. Bennett1 aYisha Lu1 aYi Zhou1 aC. Dirk Keene1 aSandra Weintraub1 aTamar Gefen1 aM.-Marsel Mesulam1 aChangiz Geula1 aMark Maienschein-Cline1 aJalees Rehman1 aOrly Lazarov00aHuman hippocampal neurogenesis in adulthood, ageing and Alzheimer’s disease  uhttps://www.nature.com/articles/s41586-026-10169-4  a1-103 aThe existence of human hippocampal neurogenesis has long been disputed1–12 and its relevance in cognition remains unknown. Recent studies have established the presence of proliferating progenitors and immature neurons and a reduction in the latter in Alzheimer’s disease (AD)11,13. However, their origin and the molecular networks that regulate neurogenesis and function are poorly understood. Here we studied human post-mortem hippocampi obtained from different cohorts: young adults with intact memory, aged adults with no cognitive impairments, aged adults with extraordinary memory capacity (SuperAgers)14,15, adults with preclinical intermediate pathology or adults with AD. Using multiomic single-cell sequencing (single-nucleus RNA sequencing and single-nuclei assay for transposase-accessible chromatin with sequencing), we analysed the profiles of 355,997 nuclei isolated from the hippocampus samples and identified neural stem cells, neuroblasts and immature granule neurons. Dysregulated neurogenesis was largely associated with changes in chromatin accessibility. Analyses of transcription factors and target gene signatures that distinguished each of the groups revealed early alterations in chromatin accessibility of neurogenic cells from individuals with preclinical AD, and such changes were even more evident in samples from individuals with AD. We identified a distinct profile of neurogenesis in SuperAgers that may reflect a ‘resilience signature’. Finally, alterations in the profile of astrocytes and CA1 neurons govern cognitive function in the ageing hippocampus. Together, our study points to a multiomic molecular signature of the hippocampus that distinguishes cognitive resilience and deterioration with ageing.  a1476-4687