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Author Notes:

Correspondence: wthu@emory.edu

WTH, MWP, and DQ were responsible for the conception and design of the study.

WTH, JCH, KDW, MWP, JW, AK, TSW, CDD, and DQ were responsible for acquisition, analysis, and interpretation of data.

WTH, JCH, KDW, MWP, and DQ were responsible for drafting the manuscript and revising it critically for important intellectual content.

All authors read and approved the final manuscript.

The authors acknowledge the following persons for assistance with enrollment: James Lah, MD, PhD; Allan Levey, MD, PhD; Chadwick Hales, MD, PhD; Angela Ashley, MD; Felicia Goldstein, PhD; and Andrea Kippels, CNP.

This study was approved by the Emory Institutional Review Board (number 66145).

Informed consent was obtained from all subjects or their authorized representatives.

WTH has a patent (assignee, Emory University) on the use of CSF p/t-tau ratio in the evaluation of frontotemporal lobar degeneration, has received research support from Avid Pharmaceuticals, and has received travel support from Eli Lilly and Hoffman-La Roche.

DQ has received research support from Medtronic and Siemens Healthcare.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Subjects:

Research Funding:

This work was supported by National Institutes of Health grants AG43885, AG42856, and AG25688.

Keywords:

  • African American
  • Amyloid
  • Dementia
  • Endothelial dysfunction
  • Mild cognitive impairment
  • Tau

Race modifies the relationship between cognition and Alzheimer's disease cerebrospinal fluid biomarkers

Tools:

Journal Title:

Alzheimer's Research and Therapy

Volume:

Volume 9, Number 1

Publisher:

, Pages 88-88

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD. Methods: We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau 181 , respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume). Results: Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau 181 (difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p = 0.001) and p-tau 181 /Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p = 0.001). The se could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH. Conclusions: Despite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans. Trial registration: ClinicalTrials.gov, NCT02089555. Retrospectively registered on 14 March 2014.

Copyright information:

© 2017 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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