Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?
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.
Available from: PubMed Central
- "of β-amyloid (Blennow et al., 1995; Motter et al., 1995). These papers reported a marked increase in CSF T-tau and P-tau accompanied by a marked decrease in Aβ42 in AD (Blennow et al., 1995; Motter et al., 1995). The following years, many research reports consistently showed that the " AD profile " of increased CSF levels of T-tau and P-tau together with decreased Aβ42 had high sensitivity and specificity, both in the range of 85–90%, to identify AD dementia, for review see (Blennow and Hampel, 2003). "
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ABSTRACT: This paper gives a short review on cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD), from early developments to high-precision validated assays on fully automated lab analyzers. We also discuss developments on novel biomarkers, such as synaptic proteins and Aβ oligomers. Our vision for the future is that assaying a set of biomarkers in a single CSF tube can monitor the whole spectrum of AD molecular pathogenic events. CSF biomarkers will have a central position not only for clinical diagnosis, but also for the understanding of the sequence of molecular events in the pathogenic process underlying AD and as tools to monitor the effects of novel drug candidates targeting these different mechanisms.
Frontiers in Neuroscience 09/2015; 9. DOI:10.3389/fnins.2015.00345 · 3.66 Impact Factor
Available from: Per Mårten Johansson
- "In all AD patients (n = 32) as well as in AD men (n = 15), only CSF IGFBP-2 level correlated or tended to correlate with CSF levels of T-tau and P-tau. CSF levels of T-tau and P-tau are typically increased in AD , reflecting axonal and neuronal damage and injury, which correlates with neurofibrillary tangle stage and the intensity of the disease process  . In transgenic mice, global overexpression of IGFBP-2 resulted in a moderate reduction of brain weight    , likely due to reduced bioavailability of IGFs by IGFBP- 2 excess. "
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Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD).
Objective and methods:
This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF).
Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 level was increased in AD men versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein.
In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
Journal of Alzheimer's disease: JAD 09/2015; 48(3). DOI:10.3233/JAD-150351 · 4.15 Impact Factor
Available from: Yvonne Freund-Levi
- "The collected CSF was used for analysis of T-tau, P-tau and Aβ1-42 at the Department of Clinical Neurochemistry, Mölndal Hospital. The T-tau concentration in CSF was determined using a sandwich ELISA (INNOTEST® hTAU Ag; Innogenetics, Gent, Belgium) specifically constructed to measure all tau isoforms irrespectively of phosphorylation status . Tau phosphorylated at threonine 181 (P-tau181) was measured using a sandwich ELISA method [INNOTEST® PHOSPHO-TAU (181P); Innogenetics] . "
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The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and Aβ1-42.
One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points).
Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95).
Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD.
08/2014; 4(2). DOI:10.1159/000363500
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