Vrednovanje određivanja ukupnih i fosforiliranih tau proteina u likvoru radi razlikovanja Alzheimerove bolesti i vaskularne demencije [Evaluation of measurement of total and phosphorylated tau proteins in cerebrospinal fluid for differentiation of Alzheimer's disease and vascular dementia]

Kiđemet-Piskač, Spomenka (2018) Vrednovanje određivanja ukupnih i fosforiliranih tau proteina u likvoru radi razlikovanja Alzheimerove bolesti i vaskularne demencije [Evaluation of measurement of total and phosphorylated tau proteins in cerebrospinal fluid for differentiation of Alzheimer's disease and vascular dementia]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Dementia is a major public health problem worldwide. The most common primary cause of dementia is Alzheimer's disease (AD) followed by vascular dementia (VaD). AD and VaD are often difficult to distinguish in their early stages in clinical practice. Because VaD can be prevented by acting on risk factors and new medications have emerged that could slow down the progression of AD, early accurate diagnosis is crucial. Available clinical criteria have not shown sufficient sensitivity and specificity in differentiatiating of AD and VaD, and better biological markers are needed. The aim of this study was to evaluate cerebrospinal fluid (CSF) levels of total tau protein, tau phosphorylated at threonine 181 (p-tau181), serine 199 (p-tau199), and threonine 231 (p-tau231) for their use in the early differentiation of AD and VaD. The study included 152 patients with AD (Mini-Mental State Examination, MMSE 15-26), 28 patients with VaD, four patients with "mixed dementia" (VaD + AD) and 18 healthy controls. The diagnostic accuracy of all investigated biomarkers showed that they may differentiate patients with AD and VaD from healthy control subjects. However none could differentiate patients with AD from patients with VaD. Only the compund factor score (FS) of p-tau231 and MMSE distinguished the patients with AD from those with VaD with statistical significance (p < 0.05), with a sensitivity higher than 75%. These data indicate that FS of p-tau231 and MMSE scores has a strong potential to provide early stage distinction between AD and VaD.

Abstract in Croatian

Demencije su jedan od glavnih javnozdravstvenih problema širom svijeta. Najčešći primarni uzrok sindroma demencije je Alzheimerova bolest (AB), nakon čega slijedi vaskularna demencija (VaD). U kliničkoj praksi je vrlo teško razlikovati AB i VaD, posebno u ranijim stadijima bolesti. Budući da se VaD može spriječiti djelovanjem na čimbenike rizika, a osim toga javljaju se novi lijekovi koji bi mogli usporiti napredovanje AB, jako je važna što ranija točna dijagnoza. Dostupni klinički kriteriji nisu pokazali dovoljnu osjetljivost i specifičnost u razlikovanju AB i VaD, stoga je potrebno pronaći bolje biološke biljege. Cilj ove studije bio je procijeniti razinu ukupnog tau proteina u likvoru i tau proteina fosforiliranih na treoninu 181 (p-tau181), serinu 199 (p-tau199) i treoninu 231 (p-tau231) te mogućnost njihovog korištenja u ranom razlikovanju AB i VaD. Istraživanje je obuhvatilo 152 bolesnika s AB (Mini-Mental State Examination, MMSE 15-26), 28 bolesnika s VaD, četiri bolesnika s "mješovitom demencijom" (VaD + AD) i 18 zdravih kontrola. Rezultati su pokazali da svi ispitivani biološki biljezi mogu razlikovati bolesnike s AB i VaD od zdravih kontrolnih ispitanika. Međutim, niti jedan od ispitivanih bioloških biljega nije imao odgovarajuću statističku snagu razlikovanja skupine bolesnika s AB od skupine bolesnika s VaD. Jedino je pomoću združenog faktorskog skora (FS) p-tau231 i MMSE bilo moguće uspješno razlikovanje skupine bolesnika s AD od onih s VaD sa dostatnom statističkom značajnošću (p < 0,05), te osjetljivošću većom od 75%. To ukazuje kako FS (p-tau231 i MMSE) ima velik potencijal u razlikovanju AB i VaD još u ranim stadijima bolesti, što treba treba potvrditi u budućim istraživanjima na još većem broju bolesnika.

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