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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), A[beta] plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF A[beta]42, 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 A[beta] plaques in the cortical biopsy had lower (p = 0.009) CSF A[beta]42 levels than those with no A[beta] plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) A[beta]42 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 A[beta]42 and highest tau and p-tau 181 levels in CSF. The A[beta]42 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 A[beta] was independently predicted by the APOE [epsilon]4 carrier status and age but not by CSF A[beta]42 or tau levels.

Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF A[beta]42 and high CSF tau and p-tau levels, respectively.

GLOSSARY: A[beta]42: 42 amino acid isoform of amyloid [beta]

AD: Alzheimer disease

CDR: Clinical Dementia Rating

DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th edition

ICP: intracranial pressure

iNPH: idiopathic normal pressure hydrocephalus

KUH: Kuopio University Hospital

NPH: normal pressure hydrocephalus

PiB: Pittsburgh compound B

t-tau: total tau

(C)2012 American Academy of Neurology