Abstract Details

Title Longitudinal Associations Between Plasma GFAP, Cognition, Amyloid Burden, and Neurodegeneration in Preclinical Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 13-010

Objective To examine whether plasma glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, predicts cognitive decline, clinical progression, and biomarker changes in preclinical Alzheimer's disease (AD), and whether these associations differ by sex or amyloid status.

Background GFAP reflects astrocyte reactivity associated with amyloid pathology and neurodegeneration in AD, but its prognostic role in the preclinical stage remains unclear.

Design/Methods Data were analyzed from 949 cognitively unimpaired participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study, a 240-week, multicenter, placebo-controlled trial of solanezumab in amyloid-positive older adults, and the companion amyloid-negative LEARN cohort. Associations between baseline plasma GFAP and longitudinal cognitive trajectories (Preclinical Alzheimer’s Cognitive Composite [PACC]), clinical progression (defined as conversion from global CDR = 0 to ≥ 0.5), amyloid PET, and structural MRI measures of neurodegeneration were examined.

Results In the A4 placebo group (Aβ+), higher baseline GFAP predicted faster PACC decline (β = –0.21 ± 0.06, p = 0.004) and greater cortical atrophy in AD-signature regions (β = –5.7 ± 2.4, p = 0.02). In the LEARN cohort (Aβ-), GFAP predicted progression to CDR > 0 (HR = 1.45, 95% CI 1.13–1.87, p = 0.008) and amyloid conversion (OR = 1.40, 95% CI 1.00–1.97, p = 0.048). Among females, GFAP was associated with both lower baseline PACC (β = –5.35 ± 1.96, p = 0.007), faster cognitive decline (β = –0.21 ± 0.05, p < 0.001), and increased risk of CDR progression (HR = 1.31, 95% CI 1.08–1.58, p = 0.005). Among males, associations were weaker, limited to PACC slope (β = –0.14 ± 0.06, p = 0.018), and not significant for clinical progression or imaging outcomes.

Conclusions

Our findings identify astrocytic activation as an early contributor to neurodegeneration and support GFAP as a candidate biomarker for precision prevention in preclinical AD.

Authors/Disclosures
Ali Ezzati, MD (University of California, Irvine) PRESENTER	The institution of Dr. Ezzati has received research support from NIA. The institution of Dr. Ezzati has received research support from Alzheimer's Association. The institution of Dr. Ezzati has received research support from Cure Alzheimer's Fund.
Babak Khorsand, PhD	Dr. Khorsand has nothing to disclose.
Elham Ghanbarian, MD, PhD	Dr. Ghanbarian has nothing to disclose.

��ɫ��

��ɫ��