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: Objective: To compare cerebrospinal fluid (CSF) biomarkers and brain structure in preclinical mutation carriers (MC) and non-carriers (NC) from families with familial Alzheimer disease (FAD). Methods: The study included members from four Swedish families at risk for carrying an APPswe, APParc, PSEN1 H163Y or PSEN1 I143T mutation. Magnetic resonance imaging (MRI) scans were obtained from 13 MC and 20 NC and analyzed using vertex-based analyses of cortical thickness and volume. CSF was collected from 10 MC and 12 NC and analyzed for Aβ42, tau-protein and phospho-tau. Results: The MC had significantly lower levels of CSF Aβ42 and higher levels tau-protein and phospho-tau than the NC. There was a trend showing a decrease in Aβ42 15 – 20 years before expected onset of clinical symptoms, while a trend of increasing tau-protein and phospho-tau was observed closer to expected onset. The MC had decreased volume on MRI in the left precuneus, superior temporal gyrus and fusiform gyrus. Conclusions: Aberrant biomarker levels in CSF as well as regional brain atrophy are present in preclinical FAD, several years before the expected onset of clinical symptoms.Journal of Alzheimer's disease: JAD 08/2014; In-press. · 3.61 Impact Factor
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ABSTRACT: Increasing evidence suggest that Alzheimer's disease (AD) is a heterogeneous disorder that includes several subtypes with different etiology and progression. Cerebrospinal fluid (CSF) is being used to find new biomarkers reflecting the complexity of the pathological pathways within this disease. We used CSF and clinical data from patients to investigate the status of asymmetric dimethyl-L-arginine, creatine, suberylglycine, and L-carnitine along AD progression. These molecules play important roles in mitochondrial function and dysfunction in mitochondrial metabolism involved in AD pathology. We found that non-APOE4 carriers show lower levels of L-carnitine in CSF early in AD. L-carnitine levels correlate with amyloid-β (Aβ)42 levels and Mini-Mental State Examination score, but do not add to the specificity or sensitivity of the classical AD CSF biomarkers, Aβ42, phospho-tau, and total-tau. Our results suggest APOE genotype-dependent differences in L-carnitine synthesis or metabolism along AD, and insinuate that L-carnitine treatments would be more beneficial for AD patients not carrying the APOE4 isoform.Journal of Alzheimer's disease: JAD 03/2014; 41(1). DOI:10.3233/JAD-132063 · 3.61 Impact Factor
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ABSTRACT: The two hallmarks of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid plaques. Neurofibrillary tangles are formed due to the hyperphosphorylation of tau protein. There is an urgent need to develop a reliable biomarker for the diagnosis of AD. Cerebrospinal fluid (CSF) is surrounding the brain and reflects the major neuropathological features in the AD brain. Diagnosis, disease progression and drug actions rely on the AD biomarkers. Mainly CSF tau and phosphorylated tau (p-Tau) have been observed to serve the purpose for early AD. Keeping in view the early appearance of p-Tau in CSF, we analyzed p-Tau levels in 23 AD, 23 Non AD type dementia (NAD), 23 Neurological control (NC) and 23 Healthy control (HC) North Indian patients. The levels of p-Tau were found to be increased in AD patients (67.87±18.05 pg/ml, SEM 3.76) compared with NAD (47.55±7.85 pg/ml, SEM 1.64), NC (34.42±4.51 pg/ml, SEM 0.94) and HC (27.09±7.18 pg/ml, SEM 1.50). The resulting sensitivity for AD with NAD was 80.27% whereas with respect to the NAD, NC and HC was 85.40%. Therefore elevated levels of p-Tau in AD can be exploited as a predictive biomarker in North Indian AD patients.11/2013; 2(11):1119-24. DOI:10.1242/bio.20135447