CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.
Seppala, T.T. MD; Nerg, O. MD; Koivisto, A.M. MD, PhD; Rummukainen, J. MD, PhD; Puli, L. MPharm; Zetterberg, H. MD, PhD; Pyykko, O.T. BM; Helisalmi, S. PhD; Alafuzoff, I. MD, PhD; Hiltunen, M. PhD; Jaaskelainen, J.E. MD, PhD; Rinne, J. MD, PhD; Soininen, H. MD, PhD; Leinonen, V. MD, PhD; Herukka, S.-K. MD, PhD
78(20):1568-1575, May 15, 2012.
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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