乌鸦传媒

Blood-based biomarkers paralleled the progression of Alzheimer's disease neurodegeneration, a large longitudinal cohort study showed.

Increases of phosphorylated tau at threonine 181 (p-tau181) in blood plasma over time were linked with progressive neurodegeneration in brain regions associated with Alzheimer's disease and cognitive decline in people with elevated brain amyloid-beta (Aβ), reported Michael Scholl, PhD, of University of Gothenburg in Sweden, and colleagues, in .

Plasma neurofilament light chain (NfL), a marker of neuronal injury, was tied to Alzheimer's disease progression independent of amyloid-β and plasma p-tau181, they added.

"This is a major step forward showing that blood tests for tau pathology and neurodegeneration have clinical value to track disease progression in patients with Alzheimer's disease," co-author Kaj Blennow, MD, PhD, also of University of Gothenburg, told 乌鸦传媒.

"Our findings have clear and novel implications for these tests both as diagnostic tools and as outcome measures in clinical trials, as we showed that measurement of p-tau181 in blood is a reliable biomarker for Alzheimer's disease specifically and NfL is a reliable marker for neurodegenerative diseases in general," Scholl added.

The study adds to the literature showing blood tests as potential game-changers in Alzheimer's disease. Previous research has shown that both p-tau181 and p-tau217 can detect Alzheimer's, but the ability of p-tau 181 to monitor disease progression has been unclear.

"Plasma p-tau181 and p-tau217 hold significant promise as blood-based biomarkers of Alzheimer's disease, both for diagnosis and prognosis," said Michelle Mielke, PhD, of the Mayo Clinic in Rochester, Minnesota, who wasn't involved with the study. "Although assessments in population-based studies are ongoing and necessary, the current research supports the utility of these markers for assessing amyloid-beta plaques and neurofibrillary tangles and predicting cognitive decline among individuals with cognitive complaints," she told 乌鸦传媒.

"The use of plasma p-tau181 and p-tau217 to screen for cognitively impaired individuals with Alzheimer's disease pathology for disease-modifying therapeutics, especially focused on amyloid-beta and tau, will significantly reduce the costs of clinical trials," Mielke added. "Currently, a lumbar puncture for the assessment of cerebrospinal fluid amyloid-beta or an amyloid PET scan are needed to ascertain whether a potential participant has amyloid pathology. Both are much more costly and invasive than a blood draw."

The study looked at data from 1,113 participants in the cohort study from 2007 to 2016. Follow-up blood sampling was performed for up to 8 years. Participants had plasma p-tau181 and NfL measurements and at least one radiolabeled fluorodeoxyglucose (FDG) PET or structural MRI scan performed at the same study visit.

The average age of the group was 74 and 89% were white. Overall, 378 people (34%) were cognitively unimpaired and 735 (66%) were cognitively impaired. Of those who were impaired, 537 people had mild cognitive impairment and 198 people had Alzheimer's dementia.

Baseline plasma p-tau181 levels were tied to cognitive decline plus concurrent and prospective neurodegeneration in Alzheimer's-characteristic brain regions on MRI and FDG-PET. Longitudinal changes in p-tau181 paralleled cognitive decline and progression of neurodegeneration in these regions.

Plasma p-tau181 and NfL were independently associated with cognition and neurodegeneration in Alzheimer's-vulnerable areas on imaging. Plasma p-tau181 specifically was linked with cognitive impairment and neurodegeneration in people who were Aβ+. Plasma NfL was tied to cognitive decline and neurodegeneration in both Aβ+ and Aβ− groups.

The study had several limitations. All data came from a single cohort which was largely white. Only about half the group had longitudinal FDG-PET scans. In addition, the ADNI study recruited participants who were relatively free of vascular pathology; it's unclear how vascular pathology might affect these findings.

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