Disclosures: Moscoso reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
January 20, 2021
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Plasma p-tau181 serves as effective marker of AD progression in longitudinal cohort

Disclosures: Moscoso reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
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Plasma phosphorylated tau at threonine 181 served as “an accessible and scalable marker” of neurodegeneration and cognitive decline specific to Alzheimer’s disease, according to findings published in JAMA Neurology.

“Recent evidence suggests that blood-based biomarkers might be useful to detect AD pathology, potentially promoting the widespread use of biomarkers in the diagnostic

workup of AD and clinical trial screening,” Alexis Moscoso, PhD, of the Institute of Neuroscience and Physiology and the Wallenberg Center for Molecular and Translational Medicine at the University of Gothenburg in Gothenburg, Sweden, and colleagues wrote. “Among candidate disease-specific biomarkers in blood, plasma phosphorylated tau at threonine 181 (p-tau181) has shown promise as a marker of disease status.”

Moscoso and colleagues analyzed data gathered from 2007 to 2016 in the AD Neuroimaging Initiative, a longitudinal, multicenter study that tracks biomarkers and grants collaborative researchers access to its data. The analysis included data from 1,113 participants (mean age, 74 years; men, 53.9%; white, 89.1%) who had plasma p-tau181 and neurofilament light measurements taken at the same visit as a fluorine-18–labeled fluorodeoxyglucose PET or structural MRI scan. Among the 66% of participants who had cognitive decline (CImp), 73.1% had mild cognitive impairment and 26.9% had Alzheimer’s disease dementia.

Longitudinal markers of neurodegeneration on imaging scans and cognitive test scores, including the Preclinical Alzheimer Cognitive Composite and Alzheimer Disease Assessment Scale–Cognitive Subscale, served as the main outcome measures.

Longitudinal plasma p-tau181 changes correlated with cognitive decline (cognitively unimpaired [CU]: r = –0.24, P < .001; CImp: r = 0.34, P < .001) as well as prospective reductions in glucose metabolism (CU: r = –0.05, P = .48; CImp: r = –0.27, P < .001) and gray matter volume (CU: r = –0.19, P < .001; CImp: r = –0.31, P < .001). These changes occurred “in highly AD-characteristic brain regions,” according to the researchers, and “were restricted to” patients who were amyloid-beta positive.

Neurofilament light also independently correlated with cognition and neurodegeneration, but the association with neurodegeneration occurred “in brain regions exceeding this AD-typical spatial pattern” among patients who were amyloid-beta negative.

In mediation analyses, Moscoso and colleagues observed that an estimated 25% to 45% of plasma p-tau181 outcomes on cognition measures were mediated by neuroimaging-derived markers of neurodegeneration, which indicated links between plasma p-tau181 and cognition regardless of these measures.

“Study findings suggest that plasma p-tau181 was an accessible and scalable marker for predicting and monitoring neurodegeneration and cognitive decline and was, unlike plasma [neurofilament light], AD specific,” the researchers wrote. “The study findings suggest implications for the use of plasma biomarkers as measures to monitor AD progression in clinical practice and treatment trials.”

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