Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct:94:60-70.
doi: 10.1016/j.neurobiolaging.2020.05.011. Epub 2020 May 29.

A longitudinal examination of plasma neurofilament light and total tau for the clinical detection and monitoring of Alzheimer's disease

Michael A Sugarman  1 , Henrik Zetterberg  2 , Kaj Blennow  3 , Yorghos Tripodis  4 , Ann C McKee  5 , Thor D Stein  6 , Brett Martin  7 , Joseph N Palmisano  7 , Eric G Steinberg  8 , Irene Simkin  9 , Andrew E Budson  10 , Ronald Killiany  11 , Maureen K O'Connor  1 , Rhoda Au  12 , Wendy Wei Qiao Qiu  13 , Lee E Goldstein  14 , Neil W Kowall  15 , Jesse Mez  16 , Robert A Stern  17 , Michael L Alosco  18
Affiliations

A longitudinal examination of plasma neurofilament light and total tau for the clinical detection and monitoring of Alzheimer's disease

Michael A Sugarman et al. Neurobiol Aging. 2020 Oct.

Abstract

We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37-0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49-0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35-2.79]), and correlated with all neuropsychological tests (r's = 0.13-0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10-0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau.

Keywords: Alzheimer's disease; Neurofilament light; Plasma biomarkers; Total tau.

PubMed Disclaimer

Conflict of interest statement

Potential Conflicts of Interests: Robert A. Stern is a member of the Mackey-White Committee of the NFL Players Association. He is a paid consultant to Biogen (Cambridge, MA, USA) and Eli Lilly (Indianapolis, IN, USA). He receives royalties for published neuropsychological tests from Psychological Assessment Resources, Inc. (Lutz, FL, USA) and is a member of the Board of Directors of King-Devick Technologies (Chicago, IL, USA). Michael L. Alosco has received honorarium as a Scientific Advisor for Corino Therapeutics, Inc. There are no other possible conflicts of interest by other co-authors on this manuscript. For the remaining authors, there are no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Mean plasma biomarker levels at baseline, separated by consensus diagnostic groups. Error bars represent the 95% confidence intervals. Values are shown as standardized log-transformed scores. *p < .01, *p < .001 based on results from ANCOVA models and post-hoc comparisons (shown in Table 2) accounting for demographic covariates and APOE ε4 carrier status.
Figure 2.
Figure 2.
Receiver operating characteristic (ROC) curves for plasma NfL and t-tau comparing the area under the curve (AUC) for diagnostic comparisons at baseline, including models for plasma NfL, t-tau, and both biomarkers combined. Each graph displays a baseline model including only demographic covariates (age, sex, education, and race) and APOE ε4 carrier status, and models adding plasma NfL, t-tau, and simultaneously including both biomarkers.
See this image and copyright information in PMC

References

    1. Albani D, Marizzoni M, Ferrari C, Fusco F, Boeri L, Raimondi I, Jovicich J, Babiloni C, Soricelli A, Lizio R, Galluzzi S, Cavaliere L, Didic M, Schonknecht P, Molinuevo JL, Nobili F, Parnetti L, Payoux P, Bocchio L, Salvatore M, Rossini PM, Tsolaki M, Visser PJ, Richardson JC, Wiltfang J, Bordet R, Blin O, Forloni G, Frisoni GB, PharmaCog C Plasma Abeta42 as a Biomarker of Prodromal Alzheimer’s Disease Progression in Patients with Amnestic Mild Cognitive Impairment: Evidence from the PharmaCog/E-ADNI Study. J Alzheimers Dis 2019; 69: 37–48. doi: 10.3233/JAD-180321 - DOI - PubMed
    1. Alosco ML, Sugarman MA, Besser LM, Tripodis Y, Martin B, Palmisano JN, Kowall NW, Au R, Mez J, DeCarli C, Stein TD, McKee AC, Killiany RJ, Stern RA. A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer’s Disease Neuropathology. J Alzheimers Dis 2018; 63: 1347–1360. doi: 10.3233/JAD-180017 - DOI - PMC - PubMed
    1. Alosco ML, Tripodis Y, Jarnagin J, Baugh CM, Martin B, Chaisson CE, Estochen N, Song L, Cantu RC, Jeromin A, Stern RA. Repetitive head impact exposure and later-life plasma total tau in former National Football League players. Alzheimers Dement (Amst) 2017; 7: 33–40. doi: 10.1016/j.dadm.2016.11.003 - DOI - PMC - PubMed
    1. Arvanitakis Z, Capuano AW, Leurgans SE, Bennett DA, Schneider JA. Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol 2016; 15: 934–943. doi: 10.1016/S1474-4422(16)30029-1 - DOI - PMC - PubMed
    1. Ashendorf L, Jefferson AL, Green RC, Stern RA. Test-retest stability on the WRAT-3 reading subtest in geriatric cognitive evaluations. J Clin Exp Neuropsychol 2009; 31: 605–610. doi: 10.1080/13803390802375557 - DOI - PMC - PubMed

Publication types