bioRxiv : the preprint server for biology · 2025
Down syndrome with Alzheimer's disease brains have increased iron and associated lipid peroxidation consistent with ferroptosis.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Thorwald Max A, Godoy-Lugo Jose A, Kerstiens Elizabeth, Garcia Gilberto, Kim Minhoo, Shemtov Sarah J, Silva Justine, Durra Salma, O'Day Peggy A, Mack Wendy J, Hiniker Annie, Vermulst Marc, Benayoun Bérénice A, Higuchi-Sanabria Ryo, Forman Henry Jay, Head Elizabeth, Finch Caleb E
Аннотация
INTRODUCTION: Cerebral microbleeds (MB) are associated with sporadic Alzheimer's Disease (AD) and Down Syndrome with AD (DSAD). Higher MB iron may cause iron mediated lipid peroxidation. We hypothesize that amyloid deposition is linked to MB iron and that amyloid precursor protein (APP) triplication increases iron load and lipid peroxidation.
METHODS: Prefrontal cortex and cerebellum of cognitively normal (CTL), AD and DSAD ApoE3,3 carriers were examined for proteins that mediated iron metabolism, antioxidant response, and amyloid processing in lipid rafts.
RESULTS: Iron was 2-fold higher in DSAD than CTL and AD. Iron storage proteins and lipid peroxidation were increased in prefrontal cortex, but not in the cerebellum. The glutathione synthesis protein GCLM was decreased by 50% in both AD and DSAD. Activity of lipid raft GPx4, responsible for membrane repair, was decreased by at least 30% in AD and DSAD.
DISCUSSION: DSAD shows greater lipid peroxidation than AD consistent with greater MBs and iron load.
METHODS: Prefrontal cortex and cerebellum of cognitively normal (CTL), AD and DSAD ApoE3,3 carriers were examined for proteins that mediated iron metabolism, antioxidant response, and amyloid processing in lipid rafts.
RESULTS: Iron was 2-fold higher in DSAD than CTL and AD. Iron storage proteins and lipid peroxidation were increased in prefrontal cortex, but not in the cerebellum. The glutathione synthesis protein GCLM was decreased by 50% in both AD and DSAD. Activity of lipid raft GPx4, responsible for membrane repair, was decreased by at least 30% in AD and DSAD.
DISCUSSION: DSAD shows greater lipid peroxidation than AD consistent with greater MBs and iron load.