Abstract
INTRODUCTION
Development of Alzheimer’s disease (AD) pathology in Down’s syndrome (DS) occurs within a compressed timeline compared to sporadic or other genetic forms of AD.
METHODS
Plasma glial fibrillary acidic protein (GFAP) and plasma pTau-217 levels were compared by AD pathophysiology (amyloid (A+) and tau (T+) positron emission tomography [PET]) in persons with DS (N = 348) and sibling controls (N = 42). Plasma GFAP, plasma pTau-217, amyloid-PET, and tau-PET levels were compared with regard to estimated years to onset of clinical symptoms (52.5 years old). We evaluated if plasma GFAP mediated the relationship between amyloid PET and plasma pTau-217 or tau PET.
RESULTS
Plasma GFAP, a measure of astrogliosis, was elevated in A+/T- and A+/T+ individuals with DS. Plasma pTau-217 was elevated in A+/T+ individuals with DS. GFAP partially mediated the relationship between amyloid-PET and tau-PET (15.3%) and amyloid-PET and plasma pTau-217 (42.1%).
DISCUSSION
Astrogliosis is a key component in the advancement of preclinical AD pathophysiology in DS.
Highlights
Amyloid may be a necessary precursor for stimulating astrocytes.
Astrogliosis may play a key role in modifications to tau phosphorylation.
Targeting neuroinflammation may only aid amyloid positive individuals.
Alzheimer’s disease timecourse is compressed in individuals with Down’s syndrome.
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This post is Copyright: Anna H. Boerwinkle,
Julie K. Wisch,
Benjamin L. Handen,
Elizabeth Head,
Mark Mapstone,
Michael S. Rafii,
Sid E. O’Bryant,
Sharon J. Krinsky‐McHale,
Florence Lai,
H. Diana Rosas,
Shahid Zaman,
Ira T. Lott,
Dana Tudorascu,
Matthew Zammit,
Adam M. Brickman,
Joseph H. Lee,
Beau M. Ances,
the Alzheimer’s Biomarker Consortium‐Down Syndrome | November 13, 2024