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Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Lantero Rodríguez J, Snellman A, Suárez-Calvet M, Blennow K, Zetterberg H, Schöll M, Alzheimer’s Disease Neuroimaging Initiative. Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease. JAMA Neurol. 2021 Apr 1;78(4):396-406. PubMed.
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Mayo Clinic
The study by Moscoso and colleagues adds to the ongoing literature demonstrating that plasma p-tau181 is a sensitive and specific marker for Alzheimer’s disease (AD) pathology and clinical diagnosis.
This study, using ADNI data, nicely highlights the prognostic utility of this plasma marker. Higher plasma P-tau181 levels were not only associated with greater declines in cognition, brain hypometabolism, and atrophy among MCI and AD participants, but also among those who were cognitively unimpaired. Thus, this work further demonstrates that plasma P-tau181 changes very early in the AD pathological process.
In addition, longitudinal change in plasma P-tau181 corresponded with change in cognition, suggesting that it may be feasible to use this marker as a surrogate endpoint in the future.
As a whole, plasma p-tau appears to be a very promising AD marker. A future research step will be to compare the different p-tau assays (e.g., SiMoA and MSD) and isoforms (e.g., p-tau181 and p-tau217) to determine which is best for a specific context of use (diagnostic vs. prognostic) or stage of the disease.
View all comments by Michelle MielkeEli Lilly
Using longitudinally collected blood samples and data from the ADNI study from over 1,000 participants, Moscoso et al. evaluate the performance of p-tau181 as a biomarker of neurodegeneration and provide NfL for comparison.
In the cognitively impaired group, the authors found p-tau181 showed associations with both longitudinal hypometabolism (FDG-PET, AD-typical Meta-ROI) and atrophy (vMRI, AD-signature ROI). The associations were numerically higher when compared with those observed for NfL. In a follow-on analysis with the groups further stratified by the presence of amyloid pathology, the authors find the association with hypometabolism and atrophy are dependent on the presence of amyloid pathology.
Voxel wise associations performed by the authors illustrate subtle differences in the relationship between the blood biomarkers and imaging markers of neurodegeneration providing further support for the AD specificity of p-tau181 and the nonspecific nature of NfL. The mediation analysis conducted indicate the association of p-tau181 with cognitive decline is not solely due to neurodegeneration, as only 25-45 percent of cognitive decline is attributed to imaging derived neurodegeneration markers.
Using this single large study, the authors provide further confirmation that p-tau181 is an Alzheimer’s disease specific biomarker that is associated with all key elements of AD (Amyloid, tau, neurodegeneration, and cognitive decline). By incorporating NfL along with the neurodegeneration imaging markers as comparators, the authors are able to demonstrate subtle differences between the markers that support the specificity or lack of specificity for AD.
Future studies exploring the influence of co-morbidities on both these plasma markers in large population-based studies may provide additional insight into factors that may lead to divergent biomarker results or aid in interpreting therapeutic response on biomarker outcomes in future studies.
View all comments by Jeffrey DageMake a Comment
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