Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects

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.

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

“…22 Due to the addition of T807 imaging well after the start of the HAB study, CSF was obtained an average of 2.03 years prior to T807 imaging (figure e-1 at Neurology.org). This delay was examined as a potential covariate in statistical models, and did not significantly contribute to models predicting regional T807 SUVR with CSF protein measures.…”

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

“…Tau release could be simply due to cell death when there is in brain trauma, AD or other neurodegenerative disease. However, CSF tau also increased along with aging in healthy humans with no evidence of neurodegeneration (30,31). Alternatively, tau secretion from neurons is a carrier-facilitated release and the carrier could be exosomes (32).…”

Predictive Value of Cerebrospinal Fluid Visinin-Like Protein-1 Levels for Alzheimer’s Disease Early Detection and Differential Diagnosis in Patients with Mild Cognitive Impairment

“…Promising AD biomarkers, such as neuroimaging and cerebrospinal fluid (CSF) biomarkers, still cannot reliably detect the disease at preclinical stages [9][10][11]. However, the results of recent longitudinal studies on cognitively normal individuals have been encouraging: AD biomarkers that represent candidates for therapeutic trials were detected in asymptomatic individuals [12,13].…”