CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
- 15 May 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 78 (20), 1568-1575
- https://doi.org/10.1212/wnl.0b013e3182563bd0
Abstract
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) 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. 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.This publication has 25 references indexed in Scilit:
- Reduced CSF turnover and decreased ventricular Aβ42 levels are relatedBMC Neuroscience, 2011
- Amyloid and tau proteins in cortical brain biopsy and Alzheimer's diseaseAnnals of Neurology, 2010
- Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascadeThe Lancet Neurology, 2010
- Relationship of Cerebrospinal Fluid Markers to11C-PiB and18F-FDDNP BindingJournal of Nuclear Medicine, 2009
- Beta Amyloid in Alzheimer's Disease: Increased Deposition in Brain Is Reflected in Reduced Concentration in Cerebrospinal FluidBiological Psychiatry, 2009
- Continuous CSF drainage in ADNeurology, 2008
- CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalusActa Neurologica Scandinavica, 2007
- Five-Year Outcome of Normal Pressure Hydrocephalus with or Without a Shunt: Predictive Value of the Clinical Signs, Neuropsychological Evaluation and Infusion TestActa Neurochirurgica, 2002
- Tau protein is a potential biological marker for normal pressure hydrocephalusPsychiatry and Clinical Neurosciences, 2000
- Clinical diagnosis of Alzheimer's diseaseNeurology, 1984