Sex and APOE epsilon4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association Nemes, S., Logan, P. E., Manchella, M. K., Mundada, N. S., La Joie, R., Polsinelli, A. J., Hammers, D. B., Koeppe, R. A., Foroud, T. M., Nudelman, K. N., Eloyan, A., Iaccarino, L., Dorsant-Ardon, V., Taurone, A., Thangarajah, M., Dage, J. L., Aisen, P., Grinberg, L. T., Jack, C. R., Kramer, J., Kukull, W. A., Murray, M. E., Rumbaugh, M., Soleimani-Meigooni, D. N., Toga, A., Touroutoglou, A., Vemuri, P., Atri, A., Day, G. S., Duara, R., Graff-Radford, N. R., Honig, L. S., Jones, D. T., Masdeu, J., Mendez, M. F., Musiek, E., Onyike, C. U., Riddle, M., Rogalski, E., Salloway, S., Sha, S. J., Turner, R. S., Wingo, T. S., Womack, K. B., Wolk, D. A., Rabinovici, G. D., Carrillo, M. C., Dickerson, B. C., Apostolova, L. G., LEADS Consortium 2023


INTRODUCTION: We used sex and apolipoprotein E epsilon4 (APOE epsilon4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD).METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE epsilon4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden.RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE epsilon4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female epsilon4 carriers. EOnonAD female epsilon4 non-carriers also had greater gray matter atrophy than female epsilon4 carriers.DISCUSSION: The effects of sex and APOE epsilon4 must be considered when studying these populations.HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E epsilon4 (APOEepsilon4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE epsilon4 carrier status on pathology burden was the most impactful in females across all cohorts.

View details for DOI 10.1002/alz.13403

View details for PubMedID 37496307