— Another step closer to clinical utility for tracking neurodegeneration
[Irony not lost on the reader: NFL ” strongly associated with brain atrophy in multiple areas, white matter alterations, and changes in global cognition,” ]
by Judy George, Senior Staff Writer, MedPage Today April 16, 2021
Two proteins in blood — plasma neurofilament light chain (NfL) and total tau — were associated with cognition and neuroimaging outcomes, strengthening their potential as blood-based biomarkers of neurodegeneration, a large longitudinal study showed.
At baseline, NfL was more strongly associated with brain atrophy in multiple areas, white matter alterations, and changes in global cognition, reported Michelle Mielke, PhD, of the Mayo Clinic in Rochester, Minnesota. The combination of elevated NfL and total tau at baseline was more strongly associated with worse global cognition and memory loss and with neuroimaging measures, including temporal cortex thickness and increased number of infarcts.
However, total tau did not add to the prognostic value of NfL over the 6-year study, Mielke said.
The findings were reported in an abstract released in advance of the American Academy of Neurology annual meeting and will be presented as part of the meeting’s Emerging Science program on April 18.
Previous research has linked elevated levels of plasma total tau and NfL with worse cognition and neuroimaging measures of cortical thickness, cortical atrophy, white matter hyperintensity, or white matter integrity, but have not compared the two proteins, Mielke noted. “The emergence of neurofilament light and total tau in recent years as candidate plasma biomarkers of neurodegeneration merits direct comparison of their relationships with cognition and neuroimaging,” she told MedPage Today.
“It is important to understand which plasma neurodegeneration marker would be most useful for clinical trials and for diagnosis or prognosis in clinical settings,” Mielke added. “Our results suggest that plasma NfL had better utility as a prognostic marker of cognitive decline and neuroimaging changes. Plasma total tau added some cross-sectional value to NfL in specific contexts related to memory performance.”
Neurodegeneration, or brain cell loss, is characteristic of many disorders including Alzheimer’s disease, vascular dementia, and Lewy body dementia. Causes and location of neurodegeneration in the brain vary with disease. “For example, in Alzheimer’s disease, amyloid plaques and neurofibrillary tangles contribute to neurodegeneration and there tends to initially be more brain cell loss in the temporal lobe,” Mielke said. “In vascular-related cognitive impairment, infarct, white matter hyperintensities, and microbleeds can contribute to cognitive changes.”
In their study, Mielke and colleagues followed 995 participants in the community-based Mayo Clinic Study of Aging who had plasma NfL and total tau measurements, cognitive assessments, and neuroimaging data. Follow-up tests were repeated about every 15 months for a median of 6.2 years. Results were similar when researchers replicated their analyses in the multicenter Alzheimer’s Disease Neuroimaging Initiative cohort of 387 people without dementia who were followed for a median of 3 years.
Having information about total tau did provide additional insights, Mielke pointed out. “For example, the combination of having both elevated NfL and total tau was more strongly associated with worse memory performance at the time of assessment,” she noted. It may be useful to add measurements of total tau to NfL as a diagnostic tool, she suggested.
But “for prognosis purposes, neurofilament light better predicted the rate of neurodegeneration and cognitive decline, regardless of what the cause of neurodegeneration might be,” Mielke said. NfL also may help determine how fast someone declines and how effective future therapies might be in slowing this decline, she added.
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