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Changes in blood levels of neurofilament light chain protein (NfL) over time may predict years of neurodegeneration before clinical symptoms appear in early stage familial Alzheimer's disease, reveal new research.
Longitudinal measurement of NfL levels in the blood can provide a reliable reading of the evolution of neurodegeneration and may constitute a "powerful instrument for the study of new treatments for Alzheimer's disease during of clinical trials "," the lead researcher Mathias Jucker, PhD, of the German Center for Neurodegenerative Diseases of Tübingen, Germany., said in a press release.
The study was published online on 21 January in Medicine of nature.
Biomarker of neurodegeneration
NfL is a structural protein that forms the internal skeleton of neurons. When neurons are damaged, NfL is released into cerebrospinal fluid (CSF) and blood. It is under study as a biomarker for many neurological diseases.
Jucker and his colleagues have studied a group of families in the predominantly hereditary Alzheimer's network that have rare genetic variants that cause early AD. They focused on 243 mutation carriers and 162 family members who did not carry the risk mutations (controls).
The researchers found that NfL accumulated in the blood long before the onset of clinical symptoms and that changes in blood levels predicted the neurodegeneration and clinical course of presymptomatic AD.
Initially, NfL levels in CSF and serum were correlated with each other and increased significantly in mutation carriers compared to non-carriers. In non-mutant carriers, blood levels of NfL were low and remained largely stable over time.
Intra-individual longitudinal badysis of NfL serum dynamics showed that NfL levels increased over time and that the annual rate of change could differentiate between carriers of non-carriers as early as 16 years before the estimated onset of symptoms. . It's almost ten years earlier than when using absolute NfL cross-sectional levels (16.2 years vs. 6.8 years before the estimated onset of symptoms), note the researchers.
"This is not the absolute concentration of neurofilaments, but its time course is significant and can predict the future course of the disease," Jucker said.
The rate of change in serum NfL was closely badociated with cortical thinning observed on MRI but less at amyloid-β deposition badessed by positron emission tomography. NfL serum was also predictive of cognitive changes badessed with the help of the mini-examination of mental status and the logical memory test.
"It will be important to confirm our findings regarding late-onset Alzheimer's disease and to define the period of time during which neurofilament changes must be evaluated in order to optimize clinical predictability." , he added.
Revolutionary research?
Commenting on the results for Medscape Medical NewsHeather Snyder, Ph.D., senior director of medical and scientific operations at the Alzheimer's Association, described the research as important and scientifically interesting.
"This protein has been badociated more generally with neurodegeneration in general, so the results obtained in this specific population of patients with Alzheimer's disease are interesting, and I am eager to see where these works will end. "she said.
Howard Fillit, MD, founding executive director and chief scientist at the Alzheimer's Drug Discovery Foundation in New York, said Medscape Medical News that the results are new.
"What's interesting is that they did not just badyze the blood levels of this neurofilament protein, but also the rate of change in blood levels, and the really new discovery that we do not have. have never seen before, is that the rate of change as one could expect, the variable is more powerful than the single transverse measurement variable ".
Observations that NfL dynamics in serum correlate with CSF levels, MRI findings, and mini-mental status review results are "validations" of ## EQU1 ## 39, information, added Fillit. "One limitation is that it is in this family genetic population, and we do not know if the results will be the same in the sporadic population," he said.
The study "creates more hope that in the next 2, 3, 4, even 5 years, we will have a blood test for Alzheimer's disease, which will really revolutionize our field as the cholesterol has revolutionized heart disease, "Fillit said.
The study was funded by the Dominantly Inherited Alzheimer Network, funded by the National Institute of Aging and the German Center for Neurodegenerative Diseases; the National Institute of Neurological Diseases and Stroke (Core) for brain imaging; the National Science Foundation; National Institutes of Health; the Swiss National Science Foundation; the National Institute of Health Research; the biomedical research center of University College London Hospitals; and the MRC Dementias Platform UK. Drs Jucker, Snyder and Fillit did not reveal any relevant financial relationship.
Nat Med. Posted online 21 January 2019. Summary
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