XXXX cerebrospinal fluid biomarker in cognitively normal subjects.

@entity195 @entity179 @entity2204
In a large multicentre sample of cognitively normal subjects, as a function of age, gender and @entity2204 genotype, we studied the frequency of abnormal cerebrospinal fluid levels of @entity195 biomarkers including: total tau, phosphorylated tau and amyloid-b1-42. 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-b1-42 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-b amyloid status (negative or positive) and @entity179 status (negative or positive) was established based on the pathological cerebrospinal fluid @entity195 cut-off values for cerebrospinal fluid amyloid-b1-42 and total tau, respectively. While gender did not affect these biomarker values, @entity2204 genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that @entity2204 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-b1-42 values and @entity2204 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, @entity179 negative and their frequency decreased to 32% at 85 years. The amyloid-positive @entity179 -negative group remained stable. The amyloid-negative @entity179 -positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by @entity2204 genotype. The amyloid-positive @entity179 -positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-b1-42 levels were already frequent in midlife and @entity2204 genotype strongly affects the levels of cerebrospinal fluid amyloid-b1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.
