title: CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease.
abstract: 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.
authors.affiliation: Dementia Research Section and Memory Clinic, Alzheimer Memorial Center, Department of Psychiatry, Ludwig-Maximilian University Munich, Germany. katharina.buerger@med.uni-muenchen.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Buerger
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.forename: Tuula
authors.initials: T
authors.lastname: Pirttilä
authors.forename: Raymond
authors.initials: R
authors.lastname: Zinkowski
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.forename: John
authors.initials: J
authors.lastname: DeBernardis
authors.forename: Daniel
authors.initials: D
authors.lastname: Kerkman
authors.forename: Cheryl
authors.initials: C
authors.lastname: McCulloch
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D019579:Neocortex / Q000737:chemistry / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D010296:Parietal Lobe / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D016875:tau Proteins