Naslov
Phospho-tau proteins in cerebrospinal fluid as markers of therapeutic progress in Alzheimer's disease

Autori
Babić, Mirjana ; Vogrinc, Željka ; Dejanović, Nenad ; Borovečki, Fran ; Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
GlowBrain Workshop „Visualization of molecular markers in the brain“

Mjesto i datum
Zagreb, Hrvatska, 29.01.2015. - 31.01.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Phospho-tau; Alzheimer's disease; therapeutic progress

Sažetak
Therapy for Alzheimer's disease (AD) is based on cholinomimetic agents and noncompetitive antagonist of glutamatergic NMDA receptors which only attenuate AD symptoms. Immunization using Aβ, the use of β- and γ-secretase inhibitors, and GSK3 inhibitors, which are currently among the most promising disease- modifying therapies, should be applied in the early stages of disease when neurodegeneration is not in an advanced stage. Because of it, much effort is dedicated to identify reliable biomarkers to enable an accurate diagnosis of AD. Three main cerebrospinal fluid (CSF) biomarkers of AD, amyloid β1-42 (Aβ1-42), total tau (t-tau), and phosphorylated forms of tau (p-tau) reflect two major neuropathological hallmarks of AD - neurofibrillary tangles and senile plaques. Elevation of p-tau is a consequence of neurofibrillary degeneration and consequent tangles formation in the brain. Beside early diagnostics of AD, determination of CSF biomarkers is necessary for monitoring of potential treatments. Reduced levels of t- and p- tau after treatment with tau-related therapeutics should indicate that a drug is working properly. Precisely, levels of p-tau in CSF should reflect the effectiveness of tau- based therapies that decrease tau protein hyperphosphorylation (GSK3β inhibitors). However, the relationship between the levels of CSF biomarkers and clinical outcome in clinical trials is still not well understood and should be further investigated. In this study we tested if p-tau181 and p-tau231 in CSF could differentiate patients with mild cognitive impairment (MCI) from healthy control with the purpose of predicting MCI progression to AD. Although the follow-up of at least 5 years is needed to assess if defined cut-off levels of CSF p-tau181 and p-tau231 truly predict MCI conversion to AD, phospho-tau proteins greatly increase specificity and sensitivity of AD diagnosis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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