Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer's disease

Age and sex are major risk factors in Alzheimer's disease (AD) with a higher incidence of the disease in females. Neuroinflammation, which is a hallmark of AD, contributes to disease pathogenesis and is inexorably linked with inappropriate microglial activation and neurodegeneration. We investigated sex-related differences in microglia in APP/PS1 mice and in post-mortem tissue from AD patients. Changes in genes that are indicative of microglial activation were preferentially increased in cells from female APP/PS1 mice and cells from males and females were morphological, metabolically and functionally distinct. Microglia from female APP/PS1 mice were glycolytic and less phagocytic and associated with increased amyloidosis whereas microglia from males were amoeboid and this was also the case in post-mortem tissue from male AD patients, where plaque load was reduced. We propose that the sex-related differences in microglia are likely to explain, at least in part, the sexual dimorphism in AD. Guillot-Sestier et al investigated sex-related differences in microglia in postmortem brain tissue from Alzheimer's Disease (AD) patients as well as in the APP/PS1 AD mouse model. They demonstrated that there was differential expression of genes associated with microglial activation and metabolism between male and female AD mice as well as differences in morphology that were also apparent in the patient post-mortem tissue, which therefore contributes to our understanding of sexual dimorphism in AD.

Automated summary

The study demonstrated sex-related differences in microglia in postmortem brain tissue from Alzheimer's disease patients and in the APP/PS1 AD mouse model, showing differential gene expression associated with microglial activation and metabolism between male and female animals. These differences were also reflected in morphology and may contribute to the understanding of sexual dimorphism in Alzheimer's disease.