CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings

Objective: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. Methods: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. Results: The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014)Aβ42but higher (p=0.015) p-tau181inCSFas compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbarCSFsamples. In multivariate analysis, the presence of corticalAβ was independently predicted by the APOE4 carrier status and age but not by CSF Aβ42 or tau levels. Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.