Min Su Kang, Canada
Douglas Hospital McGill University McGill Centre for Studies in AgingPresenter of 2 Presentations
ACTIVATED MICROGLIA IN THE MEDIAL TEMPORAL LOBE IMPOSES SEX-DEPENDENT VULNERABILITY IN ALZHEIMER’S DISEASE
Abstract
Aims
Elucidating sex-dependent mechanisms resulting in greater vulnerability in females in Alzheimer’s disease (AD) is important for therapeutic strategy and personalized medicine. Here, we aimed to elucidate the sex-dependent microglial effect on neurodegeneration and cognition using multimodal imaging biomarkers.
Methods
A total of 143 participants (50 males, 93 females; 92 CN, 32 MCI, 19 AD) from the TRIAD cohort underwent T1, 3 PET, and CDR-SB procedures. VBM was generated using the DARTEL pipeline while static [11C]PBR28, [18F]AZD4694, and [18F]MK6240 SUVR images were generated using an in-house pipeline. Then, all images were normalized to the ADNI template with 8 mm smoothing. A multiple linear regression model was used to evaluate the effect of sex on VBM, [11C]PBR28, or the relationship between VBM and [11C]PBR28. Then, the effect of VBM and [11C]PBR28 on cognition was evaluated using mediation analysis. All analyses included age, education, APOEε4, amyloid-beta, tau, and diagnosis as covariates.
Results
Females showed a significantly lower VBM while they also showed a significantly greater [11C]PBR28 SUVR in medial temporal regions compared to males. Also, there was a substantial positive association between VBM and [11C]PBR28 in the medial temporal regions only in males. Consequently, the effect of [11C]PBR28 on CDR-SB was significantly mediated by VBM in the medial temporal lobe only in males but not in females.
Conclusions
This study highlights a sex-dependent disease mechanism in medial temporal regions; males showed lower activated microglia, greater VBM, and a protective relationship between VBM and microglia on cognition after adjusting for the AD hallmarks compared to females.
LIVE DISCUSSION
