TY  - JOUR
AU  - Kennedy, James T
AU  - Wisch, Julie K
AU  - Boerwinkle, Anna H
AU  - Millar, Peter R
AU  - McKay, Nicole S
AU  - Brickman, Adam M
AU  - Chhatwal, Jasmeer P
AU  - Mendez, Patricio Chrem
AU  - Christian, Bradley T
AU  - Cohen, Anne
AU  - Cruchaga, Carlos
AU  - Daniels, Alisha
AU  - Flores, Shaney
AU  - Handen, Benjamin L
AU  - Hartley, Sigan L
AU  - Head, Elizabeth
AU  - Ibanez, Laura
AU  - Krisnsky-McHale, Sharon J
AU  - la Fougere, Christian
AU  - Lai, Florence
AU  - Laymon, Charles M
AU  - Lee, Joseph H
AU  - Lee, Jae-Hong
AU  - Levin, Johannes
AU  - Llibre-Guerra, Jorge
AU  - Aguillon, David F
AU  - Lott, Ira T
AU  - Mapstone, Mark
AU  - McDade, Eric
AU  - Morris, John
AU  - O'Bryant, Sid E
AU  - Price, Julie C
AU  - Rafii, Michael S
AU  - Roh, Jee Hoon
AU  - Rosas, H Diana
AU  - Schupf, Nicole
AU  - Supnet-Bell, Charlene
AU  - Xiong, Chengjie
AU  - Zaman, Shahid
AU  - Benzinger, Tammie L S
AU  - Gordon, Brian A
AU  - Ances, Beau M
AU  - Alzheimer's Brain Consortium - Down Syndrome
TI  - Brain volume trajectories in Down syndrome and autosomal dominant Alzheimer's disease.
JO  - Alzheimer's and dementia
VL  - 22
IS  - 1
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2026-00078
SP  - e71103
PY  - 2026
AB  - It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD), both of which are genetic forms of Alzheimer's disease (AD).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.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.ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.
KW  - Humans
KW  - Down Syndrome: pathology
KW  - Down Syndrome: diagnostic imaging
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: genetics
KW  - Male
KW  - Female
KW  - Brain: pathology
KW  - Brain: diagnostic imaging
KW  - Magnetic Resonance Imaging
KW  - Positron-Emission Tomography
KW  - Middle Aged
KW  - Longitudinal Studies
KW  - Organ Size
KW  - Adult
KW  - Disease Progression
KW  - Aged
KW  - MRI (Other)
KW  - amyloid (Other)
KW  - volume (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41549404
DO  - DOI:10.1002/alz.71103
UR  - https://pub.dzne.de/record/284043
ER  -