The mediating role of plasma glial fibrillary acidic protein in amyloid and tau pathology in Down's syndrome
Open accessAbstract
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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One study has highlighted that plasma GFAP (produced by astrocytes), raised in response to amyloid-β accumulation in the brain, may contribute to the more rapid development of tau pathology.
“One study has highlighted that plasma GFAP (produced by astrocytes), raised in response to amyloid-β accumulation in the brain, may contribute to the more rapid development of tau pathology [7].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [7]
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- Authors
- Boerwinkle, A. H., Wisch, J. K., Handen, B. L., Head, E., Mapstone, M., Rafii, M. S., O'Bryant, S. E., Krinsky‐McHale, S. J., Lai, F., Rosas, H. D., Zaman, S., Lott, I. T., Tudorascu, D., Zammit, M., Brickman, A. M., Lee, J. H., Ances, B. M., & the Alzheimer's Biomarker Consortium‐Down Syndrome
- Affiliations
- McGovern Medical School University of Texas in Houston Houston Texas USA
- Washington University in St. Louis (US)
- University of Pittsburgh (US)
- University of California, Irvine (US)
- University of Southern California (US)
- Institute for Translational Research Department of Pharmacology and Neuroscience University of North Texas Health Science Center Fort Worth Texas USA
- Department of Psychology New York State Institute for Basic Research in Developmental Disabilities Staten Island New York USA
- Harvard University (US)
- University of Cambridge (GB)
- University of Wisconsin–Madison (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Wisch, Julie K.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2024-11-13
- Volume
- 21
- Issue
- 1
- Pages
- e14359-e14359
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC11782213
- OpenAlex
- W4404326057
- Cited by
- 14
- References
- 27
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 1
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- National Institute on Aging (U01AG051406, U01AG051412, U19 AG068054‐04)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- Down syndrome, Alzheimer's disease
- MeSH terms
- Adult, Aged, Alzheimer Disease, Brain, Down Syndrome, Female, Glial Fibrillary Acidic Protein, Gliosis, Humans, Male, Middle Aged, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography
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