Cerebrospinal fluid markers in differential diagnosis of Alzheimer's disease and vascular dementia

Boban, Marina and Grbić, Kristina and Mladinov, Mihovil and Hof, Patrick R. and Süßmair, Christine and Ackl, Nibal and Stanić, Gabrijela and Bader, Benedikt and Danek, Adrian and Šimić, Goran (2008) Cerebrospinal fluid markers in differential diagnosis of Alzheimer's disease and vascular dementia. Collegium Antropologicum, 32 (Suppl.). pp. 31-36. ISSN 0350-6134

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Abstract

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia in old people. They remain difficult to differentiate in practice because of lack of sensitivity and specificity of current clinical diagnostic criteria. Recent molecular and cellular advancements indicate that the use of cerebrospinal fluid markers may improve early detection and differential diagnosis of AD. Our objective in this study was to determine diagnostic accuracy of three cerebrospinal (CSF) markers: total tau protein (t-tau), tau protein phosphorylated on threonine 181 (p-tau181) and tau protein phosphorylated on serine 199 (p-tau199). Using commercially available ELISA kits concentrations of t-tau, p-tau181 and p-tau199 were analyzed in 12 patients with probable AD, 9 patients with VaD and 12 NC subjects. The median levels of all three markers were significantly higher in AD group versus VaD and NC groups. However, when the sensitivity levels were set to 85% or higher, only t-tau and p-tau199 satisfied consensus recommendations (specificity more than 75%) when differentiating AD from VaD. In conclusion, our preliminary data on a small group of selected subjects suggest that the CSF t-tau and p-tau199 levels are useful markers for differentiating AD from VaD.

Abstract in Croatian

Alzheimerova bolest (AD) i vaskularna demencija (VaD) dva su najčešća uzroka demencije u starih ljudi. Uslijed nedostatka osjetljivosti i specifičnosti kliničkih dijagnostičkih kriterija ova se dva poremećaja još uvijek teško razlikuju u praksi. Novija saznanja iz područja molekularne i stanične biologije ukazuju da bi korištenje markera iz cerebrospinalne tekućine (CSF) moglo unaprijediti ranu detekciju i diferencijalnu dijagnozu AD. Naš je cilj u ovom istraživanju bio odrediti dijagnostičku preciznost triju markera iz CSF: ukupnog tau proteina (t-tau), tau proteina fosforiliranog na treoninu 181 (p-tau 181) i tau proteina fosforiliranog na serinu 199 (p-tau199). Upotrebom komercijalno dostupnih ELISA kitova, analizirali smo razine t-tau, p-tau181 i p-tau199 u 12 pacijenata s dijagnozom vjerojatne AD, 9 pacijenata s VaD i 12 normalnih kontrola (NC). Medijane vrijednosti razina svih triju markera bile su značajno više u skupini pacijenata s vjerojatnom AD u odnosu na VaD i NC. Ipak, kada je prilikom diferenciranja AD od VaD razina osjetljivosti postavljena na 85% ili više, samo su t-tau i p-tau199 zadovoljili međunarodno usuglašene preporučene vrijednosti (specifičnost veću od 75%). Zaključno, naši preliminarni podaci na manjoj grupi odabranih ispitanika ukazuju da su t-tau i p-tau199 iz CSF korisni markeri za rano diferenciranje AD od VaD.

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