Morphometry Patterns of Alzheimer’s and LATE Neuropathology
Date:
Video Recording: Watch on YouTube
Slides: Download
Overview
Alzheimer’s disease neuropathologic change (AD-NC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) frequently co-occur in older adults, but their distinct and overlapping neurodegeneration patterns remain difficult to disentangle - especially because LATE is currently confirmed only at autopsy. In this talk, I presented a large autopsy-confirmed study combining ex-vivo MRI with detailed neuropathology to map brain atrophy signatures associated with AD, LATE, and their comorbidity.
Methods
Using ex vivo MRI from community-based older adults who came to autopsy, we applied deformation-based morphometry (DBM) and voxel-wise statistical testing to compare atrophy patterns across AD± / LATE± groups while controlling for demographics, scanner effects, postmortem intervals, and other common co-pathologies.
Key findings
- AD-only and LATE-only groups showed prominent atrophy primarily in medial temporal lobe regions.
- AD+LATE (comorbid) cases demonstrated more extensive and widespread tissue loss than either pathology alone.
- Importantly, advanced LATE (stage 2/3) was associated with more severe anterior hippocampal atrophy than moderate/severe AD, highlighting a differential regional vulnerability.
Why it matters
These pathology-anchored atrophy patterns help clarify how AD and LATE differ in the brain and motivate the development of imaging biomarkers that can better separate mixed pathologies, improve clinical trial stratification, and refine interpretation of medial temporal atrophy in aging.
Conference photo
