CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings

• Published in: Neurology Vol. 78; no. 20; pp. 1568 - 1575
• Main Authors: SEPPÄLÄ, T. T, NERG, O, JÄÄSKELÄINEN, J. E, RINNE, J, SOININEN, H, LEINONEN, V, HERUKKA, S.-K, KOIVISTO, A. M, RUMMUKAINEN, J, PULI, L, ZETTERBERG, H, PYYKKÖ, O. T, HELISALMI, S, ALAFUZOFF, I, HILTUNEN, M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15-05-2012
• Subjects: a-beta-42; Age; Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoprotein E4; beta -Amyloid; Biological and medical sciences; biomarkers; Biopsy; Brain; Cerebrospinal fluid; Chi-Square Distribution; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia disorders; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Frontal Lobe - pathology; Fysiologi; Humans; Hydrocephalus; Longitudinal Studies; Male; Medical sciences; Middle Aged; mild cognitive impairment; Multivariate Analysis; Neurodegenerative diseases; Neurology; normal-pressure hydrocephalus; Peptide Fragments - cerebrospinal fluid; phosphorylated-tau; Physiology; Plaques; population; Pressure; Psychiatric Status Rating Scales; Statistics as Topic; Statistics, Nonparametric; Tau protein; tau Proteins - cerebrospinal fluid; Nervous system diseases; Biopsy; Alzheimer disease; Central nervous system disease; Degenerative disease; Cerebrospinal fluid; Cerebral disorder
• ISSN: 0028-3878; 1526-632X; 1526-632X
• DOI: 10.1212/WNL.0b013e3182563bd0

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.
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.
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) Aβ42 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 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 lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels.
Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.