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11-11-2021 | Neurology | News | Article

Plasma GFAP ‘a sensitive biomarker’ for early amyloid-β pathology

Author:
Shreeya Nanda

medwireNews: Plasma glial fibrillary acidic protein (GFAP) outperforms its cerebrospinal fluid (CSF) counterpart in the detection of amyloid-β (Aβ) pathology even in the early stages of Alzheimer’s disease (AD), indicates a cross-sectional study.

Plasma levels of GFAP were elevated throughout the AD continuum, and to a greater degree than CSF GFAP levels, and also distinguished between Aβ-positive and negative individuals with “a higher accuracy than CSF GFAP”, report Kaj Blennow, from the University of Gothenburg in Sweden, and collaborators in JAMA Neurology.

They believe these results “have important implications in facilitating the detection of AD, particularly in its preclinical stage”, adding that: “This earlier detection may accelerate primary and secondary prevention trials and the design of interventional studies at early stages of AD.

“Plasma GFAP, alone or in combination with other biomarkers, could be used to screen for Aβ[-positive] individuals at any stage across the AD continuum.”

The team used the Simoa HD-X (Quanterix, Billerica, Massachusetts, USA) assay to quantify plasma and CSF GFAP levels for 300 participants of the Canadian Translational Biomarkers in Aging and Dementia (TRIAD) cohort that included individuals across the whole spectrum of AD.

Compared with cognitively unimpaired Aβ-negative participants, plasma GFAP concentrations were significantly elevated for those with preclinical AD (defined as cognitively unimpaired but Aβ-positive), mild cognitive impairment (MCI) and Aβ-positivity or AD dementia after correcting for multiple comparisons, with increases of 54%, 79% and 107%, respectively.

The levels of CSF GFAP were similarly higher for the AD continuum groups than for the cognitively unimpaired Aβ-negative group, “but the group differences were not significant after correction”, say the researchers.

They also note that “[t]he effect sizes of the increases of plasma GFAP levels were always larger than those of CSF GFAP levels.”

The results were similar in a group of patients from the BioCogBank Paris Lariboisière cohort, 118 of whom had symptomatic AD (42 with MCI and Aβ-positivity, 76 with AD dementia) and 21 who were free from cognitive impairment.

And among 384 individuals at elevated AD risk from the Spanish Alzheimer’s and Families (ALFA+) study, plasma GFAP concentrations were a significant 32% higher for participants who were Aβ-positive and tau-negative than those who were Aβ-negative and tau-negative, while CSF GFAP levels were a nonsignificant 1% higher in the former group.

However, both plasma and CSF GFAP levels were significantly increased, by 60% and 77%, respectively, for individuals who were positive for Aβ and tau relative to those who were negative for both proteins.

Blennow and colleagues also report on area under the receiver operating characteristic curve (AUC) analysis using three different definitions of Aβ-positivity. The analysis showed that the AUCs for plasma GFAP to distinguish between Aβ-positive and Aβ-negative individuals ranged from 0.82 to 0.85 in the TRIAD cohort, whereas the AUC for CSF GFAP was 0.75 for all three definitions.

And the AUCs were consistently higher for plasma than CSF GFAP in the BioCogBank and ALFA+ cohorts.

Taken together, the study results suggest that “plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD”, summarise the researchers.

They conclude: “It remains unanswered which plasma biomarker (GFAP, Aβ42/40, or forms of p-tau) is more accurately associated with Aβ pathology in particular in the preclinical stage.

“A head-to-head comparison of these biomarkers in several independent cohorts is needed.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Neurol 2021; doi:10.1001/jamaneurol.2021.3671

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