Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects

Alzheimer’s Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Original languageEnglish
Pages (from-to)2701-2715
Number of pages15
JournalBrain
Volume138
Issue numberPt 9
DOIs
Publication statusPublished - Sep 2015

Bibliographical note

© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Keywords

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease/cerebrospinal fluid
  • Amyloid beta-Peptides/cerebrospinal fluid
  • Analysis of Variance
  • Apolipoproteins E/genetics
  • Cognition/physiology
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurodegenerative Diseases/etiology
  • Neuropsychological Tests
  • Peptide Fragments/cerebrospinal fluid
  • Severity of Illness Index
  • tau Proteins/cerebrospinal fluid

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