Brain volume trajectories in Down syndrome and autosomal dominant Alzheimer's disease

Kennedy, James T.; Wisch, Julie K. ; Boerwinkle, Anna H.; Millar, Peter R.; McKay, Nicole S.; Brickman, Adam M. ; Chhatwal, Jasmeer P. ; Mendez, Patricio Chrem; Christian, Bradley T. ; Cohen, Anne; Cruchaga, Carlos ; Daniels, Alisha; Flores, Shaney; Handen, Benjamin L.; Hartley, Sigan L.; Head, Elizabeth ; Ibanez, Laura; Krisnsky‐McHale, Sharon J.; Fougere, Christian la; Lai, Florence; Laymon, Charles M.; Lee, Joseph H.; Lee, Jae‐Hong; Levin, Johannes ; Llibre‐Guerra, Jorge; Aguillon, David F.; Lott, Ira T.; Mapstone, Mark; McDade, Eric M. ; Morris, John C. ; O'Bryant, Sid E.; Price, Julie C.; Rafii, Michael S.; Roh, Jee Hoon ; Rosas, H. Diana; Schupf, Nicole; Supnet‐Bell, Charlene; Xiong, Chengjie; Zaman, Shahid; Benzinger, Tammie L. S.; Gordon, Brian A. und Ances, Beau M. (2026): Brain volume trajectories in Down syndrome and autosomal dominant Alzheimer's disease. In: Alzheimer's & Dementia, Vol. 22, No. 1, e71103

Abstract

INTRODUCTION:

It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimer’s disease (ADAD), both ofwhich are genetic forms of Alzheimer’s disease (AD).

METHODS:

We compared brain volumes in DS, ADAD, and unaffected family members serving as controls. Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. Nonlinear associations between regional volumes and estimated years to clinical symptom onset (EYO) were evaluated using generalized additive mixed-models.

RESULTS:

Longitudinal data from 267 controls, 341 participants with DS, and 358 participants with ADAD were included, totaling 1908 scans. DS volumes were lower than ADAD and controls initially and dropped linearly. ADAD had similar volumes to controls until diverging, beginning at EYO -7. Amyloid was negatively associated with volume, with similar slopes in DS and ADAD.

DISCUSSION:

ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.

• Item Type: Journal article
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1552-5260
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198