Abnormal aggregates can only be formed if the tau protein is rel

Abnormal aggregates can only be formed if the tau protein is released from its sites of binding.83 In AD

patients, tau protein is present in a pathological, BIBF 1120 chemical structure hyperphosphorylated form. Incidentally, tau pathology can also be observed in other neurodegenerative diseases, but differs from tau pathology in AD patients Inhibitors,research,lifescience,medical at the molecular level.84 Tau protein was quantified in the CSF under the hypothesis that it is released extracellularly as a result of the neurodegenerative process. The methods initially available analyzed all forms of tau regardless of their phosphorylation status at specific epitopes, ie, total tau protein (t-tau). Around 50 studies have been conducted to date with some 5000 patients and controls, and have Inhibitors,research,lifescience,medical all demonstrated an increase in the concentration of t-tau in AD patients by approximately 300% compared with nondemented elderly subjects, and a systematic increase in the concentration with age was observed in the control groups.85,86 The sensitivity and specificity levels were between 80% and Inhibitors,research,lifescience,medical 90% for t-tau as well.77 In subjects younger than 50 years, the concentrations in the CSF are usually lower than 300 pg/mL, in subjects younger than 70 years lower than 450 pg/mL, and in the over 70s lower than 500 pg/mL,78 Both t-tau and Aβ42 were already significantly altered in subjects with mild cognitive impairment (MCI)

who are at increased risk of AD Inhibitors,research,lifescience,medical over time.87 Although the AD group could be differentiated from healthy controls of the same age – with a sensitivity of 85% and a specificity of 86% – using a combination of the two markers, the differential diagnosis (classification) between AD and other primary degenerative dementias was unsatisfactory (sensitivity = 85%, specificity = 58%).79 Inhibitors,research,lifescience,medical Therefore, more specific biomarkers were sought. Hyperphosphorylated tau protein (p-tau) Approximately 30 phosphorylation epitopes have been detected in AD. Around 1999, the first methods were published and demonstrated concentrations of hyperphosphorylated tau protein in the CSF. Most of ADP ribosylation factor these studies

to date have investigated tau protein hyperphosphorylated at threonine 231 (p-tau231P) and at threonine 181 (p-taul81P), and a few results have been obtained for serine 199 (p-taul99P). A correlation with neurofibrillary neocortical pathology was demonstrated for p-tau231P in the CSF,88 but not for p-taul81P.89 Single studies are available on other epitopes as well. An increase in p-tau has consistently been found in the CSF of AD patients compared with controls. Around 20 studies have been conducted on some 2000 patients and controls with sensitivity and specificity levels of between 80% and 90% . Differences have certainly been observed between the individual p-tau subtypes in distinguishing between the groups.

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