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), Abeta plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Abeta42, 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 Abeta plaques in the cortical biopsy had lower (p = 0.009) CSF Abeta42 levels than those with no Abeta plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Abeta42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Abeta42 and highest tau and p-tau 181 levels in CSF. The Abeta42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Abeta was independently predicted by the APOE epsilon4 carrier status and age but not by CSF Abeta42 or tau levels. CONCLUSIONS: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Abeta42 and high CSF tau and p-tau levels, respectively.