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Plasma GFAP associates with secondary Alzheimer's pathology in Lewy body disease.
Cousins KAQ, Irwin DJ, Chen-Plotkin A, Shaw LM, Arezoumandan S, Lee EB, Wolk DA, Weintraub D, Spindler M, Deik A, Grossman M, Tropea TF. Plasma GFAP associates with secondary Alzheimer's pathology in Lewy body disease. Annals of clinical and translational neurology. 2023 May 1; 10(5):802-813.
Within Lewy body spectrum disorders (LBSD) with a-synuclein pathology (aSyn), concomitant Alzheimer''s disease (AD) pathology is common and is predictive of clinical outcomes, including cognitive impairment and decline. Plasma phosphorylated tau 181 (p-tau ) is sensitive to AD neuropathologic change (ADNC) in clinical AD, and plasma glial fibrillary acidic protein (GFAP) is associated with the presence of ß-amyloid plaques. While these plasma biomarkers are well tested in clinical and pathological AD, their diagnostic and prognostic performance for concomitant AD in LBSD is unknown.
In autopsy-confirmed aSyn-positive LBSD, we tested how plasma p-tau and GFAP differed across aSyn with concomitant ADNC (aSyn+AD; n? = 19) and aSyn without AD (aSyn; n? = 30). Severity of burden was scored on a semiquantitative scale for several pathologies (e.g., ß-amyloid and tau), and scores were averaged across sampled brainstem, limbic, and neocortical regions.
Linear models showed that plasma GFAP was significantly higher in aSyn+AD compared to aSyn (ß? = 0.31, 95% CI? = 0.065-0.56, and P? = 0.015), after covarying for age at plasma, plasma-to-death interval, and sex; plasma p-tau was not (P? = 0.37). Next, linear models tested associations of AD pathological features with both plasma analytes, covarying for plasma-to-death, age at plasma, and sex. GFAP was significantly associated with brain ß-amyloid (ß? = 15, 95% CI? = 6.1-25, and P? = 0.0018) and tau burden (ß? = 12, 95% CI? = 2.5-22, and P? = 0.015); plasma p-tau was not associated with either (both P? > 0.34).
Findings indicate that plasma GFAP may be sensitive to concomitant AD pathology in LBSD, especially accumulation of ß-amyloid plaques.