Understanding the Microglial Immunologic Sex Differences in Alzheimer Disease: Feixiong Cheng, PhD


The assistant professor at Cleveland Clinic discussed findings from a recently published study that provided insights on the understanding of the molecular basis for female predominance in Alzheimer disease. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

"The inflammation profile in a male and female may be different. In multiple disease like heart disease and cancer, people see more inflammation and key cytokine expression in women compared with men."

As clinicians continue to uncover more about the pathology of Alzheimer disease (AD), research has shown that the disease disproportionately affects women. Not only do age-matched women comprise a higher proportion of AD cases, but they also show faster cognitive decline after a diagnosis of mild cognitive impairment or AD-related dementia. In addition, amyloid-ß levels measured with PET brain imaging and biochemical analysis of cerebrospinal fluid have shown limited sex differences.

Recently published in Alzheimer’s & Dementia, a group of investigators sought to understand the molecular mechanisms that contribute to sex differences, in particular female predominance, in AD prevalence, symptomatology and pathology. Led by senior author Feixiong Cheng, PhD, cellular metabolism and immune responses across individuals with AD were evaluated as a function of sex with diverse clinical diagnosis of cognitive status at death (cogdx), Braak staging, and Consortium to Establish a Regsitry for AD (CERAD) scores. The Religious Order Study and Rush Memory and Aging Project (ROSMAP) cohort were utilized for both metabolomics and transcriptomics data.

At the conclusion of the analysis, results showed female-specific elevation in glycerophosphorylcholine and N-acetylglutamate, which are 2 AD inflammatory metabolites involved in interleukin-17 signaling, C-type lectin receptor, interferon signaling, and Toll-like receptor pathways. Cheng, an assistant professor at Cleveland Clinic, sat down with NeurologyLive® to discuss the findings in detail, including the most significant sex-specific differences observed. Additionally, he provided comment on how the group came to these conclusions, and why previous studies may have not seen this before.

1. Hou Y, Caldwell JZK, Lathia JD, et al. Microglial immunometabolism endophenotypes contribute to sex difference in Alzheimer’s disease. Alzheim & Dement. Published November 20, 2023. doi:10.1002/alz.13546
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