Plasma GFAP Does Not Independently Predict Alzheimer Disease Progression Beyond Amyloid Burden
KEY TAKEAWAYS
- Plasma GFAP was associated with tau accumulation and hippocampal atrophy, but these relationships disappeared after accounting for amyloid burden.
- Findings from 2 longitudinal cohorts suggest GFAP reflects amyloid-associated astrocyte activation rather than independently predicting Alzheimer disease progression.
- GFAP may complement amyloid biomarkers but may not provide additional prognostic information.
Plasma glial fibrillary acidic protein (GFAP) did not independently predict Alzheimer disease (AD) progression after adjustment for cerebral amyloid burden in analyses of 2 longitudinal cohorts presented at the 2026 Alzheimer's Association International Conference (AAIC). The findings suggest that elevated GFAP primarily reflects amyloid-associated astrocytic activation rather than contributing independent prognostic information for downstream AD pathology or cognitive decline.
Investigators analyzed data from the Harvard Aging Brain Study (HABS; n=355), which enrolled cognitively unimpaired older adults with baseline plasma GFAP measurements, amyloid PET imaging, and longitudinal tau PET, MRI, and cognitive assessments. Results were validated in the Religious Orders Study/Memory and Aging Project (ROSMAP; n=610), which included brain GFAP mRNA expression, postmortem amyloid and tau pathology, and longitudinal cognitive data. Models were evaluated before and after adjustment for amyloid burden.
What the Data Showed
- In HABS, higher baseline plasma GFAP was associated with greater longitudinal tau accumulation (P=.025) and hippocampal volume loss (P=.018), but both associations were fully attenuated after adjustment for amyloid burden.
- Plasma GFAP was not associated with longitudinal cognitive decline.
- In ROSMAP, higher brain GFAP expression was associated with greater tau pathology (P=.012) and faster cognitive decline (P=2.5×10⁻³), but these associations were eliminated or reduced to borderline significance after amyloid adjustment.
The investigators concluded that GFAP may serve as a complementary biomarker of amyloid pathology alongside phosphorylated tau 217 (pTau217), but it did not provide independent prognostic value for tau pathology, neurodegeneration, or cognitive decline in these cohorts.
Source
Danziger R, Kivisakk P, Teng L, et al. Is GFAP an Independent Predictor of Alzheimer Disease Progression? Convergent Evidence from Two Longitudinal Cohorts. Poster presented at the Alzheimer's Association International Conference (AAIC); July 12–15, 2026; London, United Kingdom, and online.