Alzheimer's & dementia : the journal of the Alzheimer's AssociationSep 8, 2021

Blood markers for detecting and predicting early Alzheimer's disease

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

Plasma GFAP levels were notably higher in cognitively unimpaired older adults with brain amyloidosis (Aβ+) compared to those without (Aβ-).

GFAP demonstrated the highest effect size and area under the curve (AUC) for distinguishing between Aβ+ and Aβ- individuals.
While GFAP, p-tau181, and p-tau231 showed similar AUCs, all were significantly higher than that of neurofilament light (NFL).
The combination of GFAP with a base model including age, sex, and APOE ε4 status achieved an AUC greater than 90%.
Longitudinally, GFAP and p-tau181 levels increased in Aβ+ individuals, while NFL levels rose in Aβ- individuals over 12 months.
GFAP, p-tau181, p-tau231, and NFL correlated significantly with cognitive performance, but not with hippocampal volume.

Simplified

INTRODUCTION: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).

METHODS: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.

RESULTS: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.

DISCUSSION: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

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Blood markers for detecting and predicting early Alzheimer's disease

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