Vrijednost određivanja ukupnog i fosforiliranog tau proteina iz likvora u diferencijalnoj dijagnozi sindroma demencije

doctoral thesis

• Title (english): CSF total tau phosphorylated tau proteins in the differential diagnosis of dementia
• Author: Marina Boban; MBZ: 277094
• Mentor: Goran Šimić (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2009-12-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

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%).

Abstract (english)

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.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:355664
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 105 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 06:51:39