White matter aging across the lifespan in Down syndrome: developmental origins, Alzheimer's disease progression, and therapeutic implications

npj Dementia 2026 Open access

Read full text
Authors: Justine Silva, Jr-Jiun Liou, Simren Parikh, Natalie C. Edwards, Julia Kofler, M. D. Ikonomovic, Florence Lai, H. Diana Rosas, David K. Powell, Frederick A. Schmitt, Patrick J. Lao, Donna M. Wilcock
+2 more Adam M. Brickman, Elizabeth Head
DOI: 10.1038/s44400-026-00062-2
Cited by: 2
References: 64

Abstract

Abstract People with Down syndrome (DS) develop Alzheimer’s disease (AD) neuropathology by the age of 40 years, with cognitive decline common after age 50. While amyloid precursor protein overexpression due to trisomy 21 is a major driver of AD pathology, increasing evidence indicates that DS-related white matter aging involves broader mechanisms beyond amyloid. This review synthesizes neuropathological, neuroimaging, molecular, and fluid biomarker studies linking white matter pathology to cognition in DS.

Fields of Study & Subjects

Down syndrome and intellectual disability research Genetic Neurodegenerative Diseases Cell Image Analysis Techniques

Publication details

Journal / source
npj Dementia
Publisher
Springer Science and Business Media LLC
Volume
2
Issue
1
Publication date
26 February 2026
Language
EN