CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease.
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.
Buerger
Katharina
K
Dementia Research Section and Memory Clinic, Alzheimer Memorial Center, Department of Psychiatry, Ludwig-Maximilian University Munich, Germany. katharina.buerger@med.uni-muenchen.de
Ewers
Michael
M
Pirttilä
Tuula
T
Zinkowski
Raymond
R
Alafuzoff
Irina
I
Teipel
Stefan J
SJ
DeBernardis
John
J
Kerkman
Daniel
D
McCulloch
Cheryl
C
Soininen
Hilkka
H
Hampel
Harald
H
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*
D015415:Biomarkers; D016875:tau Proteins