Age and sex are associated with Alzheimer's disease neuropathology in Down syndrome

Authors

• Elizabeth J. Andrews, University of California Irvine
• Phong T. Ngo, University of California Irvine
• Jesse R. Pascual, University of California Irvine
• Freddy Gonzalez, University of California Irvine
• Michael Phelan, University of California Irvine
• Sierra T. Wright, University of California Irvine
• Jordan Harp, University of KentuckyFollow
• Frederick Schmitt, University of KentuckyFollow
• Florence Lai, Harvard University
• Patrick J. Lao, Columbia University Medical Center
• Adam M. Brickman, Columbia University Medical Center
• Julia Kofler, University of Pittsburgh
• Milos D. Ikonomovic, University of Pittsburgh
• Elizabeth Head, University of California IrvineFollow

Abstract

INTRODUCTION: This study investigates the association of age and biological sex with Alzheimer's disease (AD) neuropathology in Down syndrome (DS). METHODS: We examined the frontal/occipital cortex in people with DS (n = 14/13, 1–39 years), DS with AD (DSAD) neuropathology (n = 18/19, 42–61 years), late-onset AD (n = 15/16, 72–96 years), and age-matched controls (n = 50/47)(n = 156). The area occupied by AT8 and 6E10 immunolabeling, representing tangle and plaque loads, respectively, was used for segmented linear regression analyses. RESULTS: There was elevated neuropathology after age 35 in DSAD, with inflection points at ∼31 years (amyloid-β [Aβ]) and ∼28 (phosphorylated tau [p-tau]) in the frontal cortex and ∼36 years (both Aβ and p-tau) in the occipital cortex. Occipital p-tau was higher in women relative to men with DS. Aβ and p-tau pathology were correlated in women with DS but not in men with DS in the occipital cortex. DISCUSSION: Women with DS may show a more advanced stage of tau pathology relative to men with DS. Highlights: Amyloid-β (Aβ) and phosphorylated tau (p-tau) Alzheimer's disease (AD) pathology emerge after 30 years of age in the frontal cortex, followed 7 years later by pathology in the occipital cortex in Down syndrome (DS). Women with DS show a more rapid progression of AD neuropathology seen by trends in higher p-tau relative to men, despite similar levels of Aβ. Women with DS show a stronger association between Aβ and tau in the occipital but not frontal cortex relative to men with DS, independent of age.

Document Type

Article

Publication Date

7-1-2025

Notes/Citation Information

Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Digital Object Identifier (DOI)

10.1002/alz.70408

Archival?

Archival

Repository Citation

Andrews, Elizabeth J.; Ngo, Phong T.; Pascual, Jesse R.; Gonzalez, Freddy; Phelan, Michael; Wright, Sierra T.; Harp, Jordan; Schmitt, Frederick; Lai, Florence; Lao, Patrick J.; Brickman, Adam M.; Kofler, Julia; Ikonomovic, Milos D.; and Head, Elizabeth, "Age and sex are associated with Alzheimer's disease neuropathology in Down syndrome" (2025). Psychology Faculty Publications. 300.
https://uknowledge.uky.edu/psychology_facpub/300