Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?
ABSTRACT Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.
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ABSTRACT: The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD.Frontiers in Cellular Neuroscience 11/2014; fncel.2014.00369. eCollection 2014.. DOI:10.3389/fncel.2014.00369 · 4.18 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia and is characterized by neuroaxonal and synaptic degeneration accompanied by intraneuronal neurofibrillary tangles and accumulation of extracellular plaques in specific brain regions. These features are reflected in the AD cerebrospinal fluid (CSF) by increased concentrations of total tau (t-tau) and phosphorylated tau (p-tau), together with decreased concentrations of β-amyloid (Aβ42), respectively. In combination, Aβ42, p-tau and t-tau are 85-95% sensitive and specific for AD in both prodromal and dementia stages of the disease and they are now included in the diagnostic research criteria for AD. However, to fully implement these biomarkers into clinical practice, harmonization of data are needed. This work is ongoing through the standardization of analytical procedures between clinical laboratories and the production of reference materials for CSF Aβ42, p-tau and t-tau. To monitor other aspects of AD neuropathology, e.g., synaptic dysfunction and/or to develop markers of progression, identifying novel candidate biomarkers is of great importance. Based on knowledge from the established biomarkers, exemplified by Aβ and its many variants, and emerging data on neurogranin fragments as biomarker candidate(s), a thorough protein characterization in order to fully understand the diagnostic value of a protein is a suggested approach for successful biomarker discovery. Copyright © 2015. Published by Elsevier B.V.Clinica Chimica Acta 02/2015; DOI:10.1016/j.cca.2015.01.041 · 2.76 Impact Factor
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ABSTRACT: Background Familial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 and APP is associated with changes in the brain.Objective The aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD.SubjectsTen mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 non-carriers (NCs) were included in the study. Three MCs were symptomatic and seven were pre-symptomatic (pre-MCs).Methods Whole-brain GM volume as well as fractional anisotropy (FA) and mean diffusivity (MD) using voxel-based morphometry and tract-based spatial statistics analyses respectively were compared between MCs and NCs. FA and MD maps were obtained from diffusion tensor imaging.ResultsA significant increase in MD was found in the left inferior longitudinal fasciculus, cingulum and bilateral superior longitudinal fasciculus in pre-MCs compared to NCs. After inclusion of the three symptomatic MCs in the analysis, the regions became wider. The mean MD of these regions showed significant negative correlation with the CSF level of Aβ42, and positive correlations with P-tau181p and T-tau. No differences were observed in GM volume and FA between the groups.Conclusions The results of this study suggest that FAD gene mutations affect WM diffusivity before changes in GM volume can be detected. The WM changes observed were related to changes in the CSF, with similar patterns previously observed in sporadic Alzheimer's disease.This article is protected by copyright. All rights reserved.Journal of Internal Medicine 01/2015; DOI:10.1111/joim.12352 · 5.79 Impact Factor