2026-07-23T17:12:31Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/187022024-02-27T15:09:02Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc O'Neill, Eoin author Mela, Virginia author Gaban, Aline Sayd author Bechet, Sibylle author McGrath, Aoife author Walsh, Aife author McIntosh, Allison author Lynch, Marina A author 2022-07-05 Many studies implicate microglia in the pathogenesis of Alzheimer's disease (AD) but precisely how these cells make their impact has not been determined to date. One contributory factor is likely to be the enhanced production of inflammatory mediators and it is now known that microglia with this secretory phenotype exhibit other adaptations including in their morphology, function, and metabolism. AD, like many neurological disorders, demonstrates a sex bias and recent evidence indicates that the sexual dimorphism in microglial function, which has been recognized for many years in early development, persists into adulthood and aging. Here, we demonstrate sex-related differences in microglia from post mortem tissue of male and female AD patients and a marked increase in the number of dystrophic and rod-shaped microglia in tissue from female AD patients compared with males. Furthermore, there was an increase in iron-laden microglia in tissue from female AD patients and this has been reported to reflect mitochondrial changes. To address this further, we assessed changes in microglia from male and female APP/PS1 mice and demonstrate that iron accumulation in microglia is increased to a greater extent in tissue prepared from females compared with males. This was associated with altered expression of genes coding for proteins that modulate mitochondrial function. The findings suggest that sex-related differences in the severity and perhaps incidence of AD may, at least in part, arise from sexual dimorphism in microglia. 10.3389/fncel.2022.939830 1662-5102 Frontiers in cellular neuroscience http://hdl.handle.net/10668/20638 35875349 http://hdl.handle.net/20.500.12105/18702 Alzheimer’s disease iron accumulation microglia mitochondrial dysfunction sex-related differences Sex-Related Microglial Perturbation Is Related to Mitochondrial Changes in a Model of Alzheimer's Disease.