Brain Advance Access originally published online on September 29, 2006
Brain 2006 129(11):3035-3041; doi:10.1093/brain/awl269
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CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease
1 Dementia Research Section and Memory Clinic, Alzheimer Memorial Center, Department of Psychiatry, Ludwig-Maximilian University Munich, Germany 2 Department of Neuroscience and Neurology Kuopio, Finland 3 Department of Pathology, Kuopio University Hospital, University of Kuopio Kuopio, Finland 4 Applied NeuroSolutions Inc., Vernon Hills IL, USA
Correspondence to: Katharina Buerger, MD, Dementia Research Section and Memory Clinic, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany E-mail: katharina.buerger{at}med.uni-muenchen.de
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.
Key Words: hyperphosphorylated tau protein; CSF; neuropathology; Alzheimer's disease
Abbreviations: HP-tau, hyperphosphorylated tau; NFTs, neurofibrillary tangles; NPs, neuritic plaques; P-tau231P, P-tau phosphorylated at threonine 231
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Received August 7, 2006. Revised August 30, 2006. Accepted August 31, 2006.
*These authors contributed equally to this work.
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