biostudies-literatureUnknownGomez-Pascual ANIA NIH HHSIn aged humans and mice, aggregates of hypobranched glycogen molecules called polyglucosan bodies (PGBs) accumulate in hippocampal astrocytes. PGBs are known to drive cognitive decline in neurological diseases but remain largely unstudied in the context of typical brain aging. Here, we show that PGBs arise in autophagy-dysregulated astrocytes of the aged C57BL/6J mouse hippocampus. To map the genetic cause of age-related PGB accumulation, we quantified PGB burden in 32 fully sequenced BXD-recombinant inbred mouse strains, which display a 400-fold variation in hippocampal PGB burden at 16-18 months of age. A major modifier locus was mapped to chromosome 1 at 72-75 Mb, which we defined as the <i>Pgb1</i> locus. To evaluate candidate genes and downstream mechanisms by which <i>Pgb1</i> controbioRxiv : the preprint server for biology2023.11.22.567373https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690248biostudies-literatureThe <i>Pgb1</i> locus controls glycogen aggregation in astrocytes of the aged hippocampus without impacting cognitive function.PMC10690248R01 AG075818R01 AG070913R01 AG075813Mozhui KOverall RWKempermann GKillmar JTomkins JEWilliams RWGlikman DMNg HXWilliams EGOhlenschlager OLu LAshbrook DGIngram DKGomez-Pascual AAebersold Rde Bakker DEMKaczorowski CJucker MXu YfalseThe <i>Pgb1</i> locus controls glycogen aggregation in astrocytes of the aged hippocampus without impacting cognitive function.In aged humans and mice, aggregates of hypobranched glycogen molecules called polyglucosan bodies (PGBs) accumulate in hippocampal astrocytes. PGBs are known to drive cognitive decline in neurological diseases but remain largely unstudied in the context of typical brain aging. Here, we show that PGBs arise in autophagy-dysregulated astrocytes of the aged C57BL/6J mouse hippocampus. To map the genetic cause of age-related PGB accumulation, we quantified PGB burden in 32 fully sequenced BXD-recombinant inbred mouse strains, which display a 400-fold variation in hippocampal PGB burden at 16-18 months of age. A major modifier locus was mapped to chromosome 1 at 72-75 Mb, which we defined as the <i>Pgb1</i> locus. To evaluate candidate genes and downstream mechanisms by which <i>Pgb1</i> contro2024-01-01T00:00:00Z2024 Jul2025-08-27T03:06:52.72Z2025-04-05T23:55:44.342ZS-EPMC106902483804533910.1101/2023.11.22.567373