Toledo JB Zetterberg H van Harten AC Glodzik L Martinez-Lage P Bocchio-Chiavetto L Rami L Hansson O Sperling R Engelborghs S Osorio RS Vanderstichele H Vandijck M Hampel H Teipl S Moghekar A Albert M Hu WT Monge Argilés JA Gorostidi A Teunissen CE De Deyn PP Hyman BT Molinuevo JL Frisoni GB Linazasoro G de Leon MJ van der Flier WM Scheltens P Blennow K Shaw LM Trojanowski JQ 2015 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. application/pdf https://sonar.ch/global/documents/46441 eng info:eu-repo/semantics/altIdentifier/doi/10.1093/brain/awv199 info:eu-repo/semantics/altIdentifier/pmid/26220940 info:eu-repo/semantics/openAccess Brain : a journal of neurology. - 2015 Alzheimer’s disease biomarkers cognitive ageing dementia imaging Adult Age Factors Aged Aged, 80 and over Alzheimer Disease Amyloid beta-Peptides Analysis of Variance Apolipoproteins E Cognition Cohort Studies Female Humans Male Middle Aged Neurodegenerative Diseases Neuropsychological Tests Peptide Fragments Severity of Illness Index tau Proteins Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects. http://purl.org/coar/resource_type/c_6501