HAI Book 2025 - Flipbook - Page 689
Galbraith, Jordan
169
Sex differences in synaptic loss in early Alzheimer9s disease
Jordan Galbraith1, Hamid Abuwarda1, Ryan O9Dell2, Adam Mecca2, Christopher van Dyck2,
Carolyn Fredericks1
1
Department of Neurology, Yale School of Medicine, New Haven, CT, US
Alzheimer’s Disease Research Unit, Yale School of Medicine, New Haven, CT, US
2
Background: Synaptic loss is an important early structural marker in Alzheimer9s disease (AD) and correlates with
cognitive decline. With the development of [11C]UCB-J, a tracer that targets synaptic vesicle glycoprotein 2A
(SV2A), we have begun to study synaptic alterations in AD in vivo. Women face twice the lifetime risk and a more
aggressive course of AD than men, and while prior postmortem work in rodents and humans has demonstrated
sex differences in spine density, synaptic morphology, and molecular synapse composition, there are no current
in vivo studies exploring sex differences in SV2A binding in AD.
Methods: [11C]UCB-J binding was measured in 37 amyloid-positive cognitively impaired (CI) participants (14 aMCI
and 23 mild dementia) and 17 amyloid-negative cognitively normal (CN) participants aged 50-85 years. Distribution
volume ratios (DVR) were calculated using a cerebellar reference region. Cluster-corrected two sample t-tests
comparing SV2A in females and males were calculated in both CI (19 female, 18 male) and CN groups (9 female, 8
male).
Results: There was higher synaptic density in CI and CN females than males in the amygdala, thalamus, head of
the caudate, and parahippocampal gyrus (p
