Vrijednost određivanja ukupnog i fosforiliranog tau proteina iz likvora u diferencijalnoj dijagnozi sindroma demencije [CSF total tau phosphorylated tau proteins in the differential diagnosis of dementia]

Boban, Marina (2009) Vrijednost određivanja ukupnog i fosforiliranog tau proteina iz likvora u diferencijalnoj dijagnozi sindroma demencije [CSF total tau phosphorylated tau proteins in the differential diagnosis of dementia]. PhD thesis, Sveučilište u Zagrebu.

Preview

PDF Download (2MB) | Preview

Abstract

Alzheimer's disease (AD) and frontotemporal dementia (FTD) represent an important differential diagnostic problem in clinical practice. The identification for new biomarkers that would help establishing the diagnosis and primary cause of the dementia is therefore of great relevance. The aim of this study was to investigate the diagnostic accuracy of three potential CSF biomarkers, total tau protein (t-tau), tau protein phosphorylated at threonine 181 (p-tau181) and tau protein phosphorylated at serine 199 (p-tau199) in the differential diagnosis of AD and FTD patients in relatively young age groups. The concentrations of these three CSF biomarkers were measured in 25 FTD patients, 27 AD patients and 25 control subjects. The CSF concentrations of all three markers were significantly higher in AD than in FTD patients (p < 0.001) or control subjects (p < 0.001). No difference was observed in FTD patient group compared to controls, except for p-tau181 (p = 0.028). When sensitivity was set at 85% or higher, specificity in differentiation between FTD and AD patients reached 40,0% for t-tau, 37,5% for p-tau181 and 56,0% for p-tau199. Improvement of the diagnostic accuracy upon logistic regression analysis with t-tau and p-tau199 as independent variables showed that 22 out of 25 FTD patients could be correctly classified. In conclusion, none of the markers per se fulfilled the criteria for the „ideal“ marker (sensitivity and specificity higher than 85%). However, combination of t-tau and p-tau199 detected correctly 88% of FTD patients, thus largely satisfying practical requirements.

Abstract in Croatian

Alzheimerova bolest (AB) i frontotemporalna demencija (FTD) predstavljaju važan diferencijalno dijagnostički problem u svakodnevnoj kliničkoj praksi. Stoga postoji potreba pronalaska bioloških markera kojima bi se pospješila točnost postavljanja dijagnoze. Cilj je ove disertacije bio ocijeniti dijagnostičku važnost triju potencijalnih markera iz likvora: ukupnog tau proteina (t-tau), tau proteina fosforiliranog na treoninu 181 (p-tau181) i tau proteina fosforiliranog na serinu 199 (p-tau199) u diferencijalnoj dijagnozi bolesnika s AB i FTD podudarnih dobnih skupina. Koncentracije navedenih proteina iz likvora određene su u 25 bolesnika s FTD, 27 bolesnika s AB te 25 ispitanika kontrolne skupine. Vrijednosti t-tau, ptau181 i p-tau199 iz likvora su bile značajno veće u skupini bolesnika s AB nego u skupini bolesnika s FTD (p<0,001) i kontrolnoj skupini (p<0,001), dok je statistički značajna razlika između bolesnika s FTD i ispitanika kontrolne skupine nađena samo za p-tau181 (p = 0,028). Kad je osjetljivost postavljena na vrijednost 85% ili više, specifičnost pri razlikovanju bolesnika s AB i FTD iznosila je 40,0% za t-tau, 37,5% za p-tau181 i 56,0% za p-tau199, čime nijedan od ovih markera nije zadovoljio kriterije radne skupine za markere (osjetljivost i specifičnost >85%). Ipak, upotrebom kombinacije vrijednosti koncentracija t-tau i p-tau199 markera iz likvora postignuta je točna klasifikacija 22 od 25 bolesnika s FTD. Zaključeno je da nijedan od navedenih markera zasebno nije pokazao karakteristike „idealnog“ markera, ali je kombinacija ttau i p-tau199 detektirala zadovoljavajuće visoki postotak FTD bolesnika (88%).

Actions (login required)

View Item

Downloads