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

• Published in: Brain (London, England : 1878) Vol. 129; no. 11; pp. 3035 - 3041
• Main Authors: Buerger, Katharina, Ewers, Michael, Pirttilä, Tuula, Zinkowski, Raymond, Alafuzoff, Irina, Teipel, Stefan J., DeBernardis, John, Kerkman, Daniel, McCulloch, Cheryl, Soininen, Hilkka, Hampel, Harald
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2006; Oxford Publishing Limited (England)
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Biological and medical sciences; Biomarkers - cerebrospinal fluid; CSF; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Frontal Lobe - chemistry; Frontal Lobe - pathology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - pathology; Humans; hyperphosphorylated tau protein; Male; Medical sciences; Neocortex - chemistry; Neocortex - pathology; Nervous system (semeiology, syndromes); Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurology; neuropathology; Parietal Lobe - pathology; Pathology; Patologi; Phosphorylation; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; tau Proteins - analysis; tau Proteins - cerebrospinal fluid; Temporal Lobe - pathology; Phosphorylation; Nervous system diseases; Alzheimer disease; hyperphosphorylated tau protein; Cerebrospinal fluid; Cerebral disorder; Anatomic pathology; Tau protein; Central nervous system disease; CSF; Degenerative disease; Alzheimer's disease; neuropathology
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awl269

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.