Journal Article

CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease

Katharina Buerger, Michael Ewers, Tuula Pirttilä, Raymond Zinkowski, Irina Alafuzoff, Stefan J. Teipel, John DeBernardis, Daniel Kerkman, Cheryl McCulloch, Hilkka Soininen and Harald Hampel

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 11, pages 3035-3041
ISSN: 0006-8950
Published online September 2006 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl269
CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease

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Hyperphosphorylated tau protein (P-tau) in CSF is a core biomarker candidate of Alzheimer's disease. Hyperphosphorylation of tau is thought to lead to neurofibrillary changes, a neuropathological hallmark of this type of dementia. Currently, the question is unresolved whether CSF levels of P-tau reflect neurofibrillary changes within the brain of a patient with the illness. Twenty-six patients were included with intra-vitam CSF as well as post-mortem neuropathological data. In the CSF, P-tau phosphorylated at threonine 231 (P-tau231P) was analysed. Post-mortem, scores of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed in frontal, temporal, parietal and hippocampal cortical areas. In the same cortical regions, load of hyperphosphorylated tau protein (HP-tau load) was determined. Concentrations of P-tau231P were measured in frontal cortex homogenates. We found significant correlations between CSF P-tau231P concentrations and scores of NFTs and HP-tau load in all neocortical regions studied. The score of NPs was correlated with CSF P-tau231P only within the frontal cortex. There was a correlation between P-tau231P in CSF and brain homogenates. These findings indicate that CSF P-tau231P may serve as an in vivo surrogate biomarker of neurofibrillary pathology in Alzheimer's disease.

Keywords: hyperphosphorylated tau protein; CSF; neuropathology; Alzheimer's disease

Journal Article.  3815 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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