Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

Suzanne E Schindler; Thomas K Karikari; Nicholas J Ashton; Rachel L Henson; Kevin E Yarasheski; Tim West; Mathew R Meyer; Kristopher M Kirmess; Yan Li; Benjamin Saef; Krista L Moulder; David Bradford; Anne M Fagan; Brian A Gordon; Tammie L S Benzinger; Joyce Balls-Berry; Randall J Bateman; Chengjie Xiong; Henrik Zetterberg; Kaj Blennow; John C Morris

doi:10.1212/WNL.0000000000200358

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

Neurology. 2022 Jul 19;99(3):e245-e257. doi: 10.1212/WNL.0000000000200358. Epub 2022 Apr 21.

Authors

Suzanne E Schindler¹, Thomas K Karikari², Nicholas J Ashton², Rachel L Henson², Kevin E Yarasheski², Tim West², Mathew R Meyer², Kristopher M Kirmess², Yan Li², Benjamin Saef², Krista L Moulder², David Bradford², Anne M Fagan², Brian A Gordon², Tammie L S Benzinger², Joyce Balls-Berry², Randall J Bateman², Chengjie Xiong², Henrik Zetterberg², Kaj Blennow², John C Morris²

Affiliations

¹ From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China. [email protected].
² From the Department of Neurology (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., J.B.-B., R.J.B., J.C.M), Knight Alzheimer Disease Research Center (S.E.S., R.L.H., Y.L., B.S., K.L.M., D.B., A.M.F., B.A.G., T.L.S.B., J.B.-B., R.J.B., C.X., J.C.M.), Hope Center for Neurological Disorders (A.M.F.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Division of Biostatistics (C.X.), Washington University School of Medicine, St. Louis, MO; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry (T.K.K., N.J.A., H.Z., K.B.), Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry (T.K.K.), University of Pittsburgh, PA; Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg, Sweden; Institute of Psychiatry, Psychology and Neuroscience (N.J.A.), Maurice Wohl Institute Clinical Neuroscience Institute, King's College London,; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), London, UK; C2N Diagnostics (K.E.Y., T.W., M.R.M., K.M.K.), St. Louis, MO; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, London,; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.

Abstract

Background and objectives: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.

Methods: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, APOE ε4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively.

Results: There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were APOE ε4 carriers, and 91% were cognitively normal. AA were less likely than NHW participants to have brain amyloidosis by CSF Aβ42/Aβ40 (22% vs 43% positive; p = 0.003). The receiver operating characteristic area under the curve of CSF Aβ42/Aβ40 status with the plasma biomarkers was as follows: Aβ42/Aβ40, 0.86 (95% CI 0.79-0.92); p-tau181, 0.76 (0.68-0.84); p-tau231, 0.69 (0.60-0.78); and NfL, 0.64 (0.55-0.73). In models predicting CSF Aβ42/Aβ40 status with plasma Aβ42/Aβ40 that included covariates (age, sex, APOE ε4 carrier status, race, and cognitive status), race did not affect the probability of CSF Aβ42/Aβ40 positivity. In similar models based on plasma p-tau181, p-tau231, or NfL, AA participants had a lower probability of CSF Aβ42/Aβ40 positivity (odds ratio 0.31 [95% CI 0.13-0.73], 0.30 [0.13-0.71], and 0.27 [0.12-0.64], respectively). Models of amyloid PET status yielded similar findings.

Discussion: Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / diagnosis
Amyloid
Amyloid beta-Peptides / metabolism
Amyloidosis* / diagnosis
Apolipoprotein E4
Biomarkers
Brain / diagnostic imaging
Humans
Intermediate Filaments
Peptide Fragments / metabolism
Phosphorylation
tau Proteins

Substances

Amyloid
Amyloid beta-Peptides
Apolipoprotein E4
Biomarkers
Peptide Fragments
amyloid beta-protein (1-40)
amyloid beta-protein (1-42)
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding