engleski

Phosphorylated tau epitopes threonin 231 and threonin 181 in the early diagnosis of Alzheimer's disease

Abnormal hyperphosphorylation of the microtubule-associated protein tau and its incorporation into neurofibrillary tangles are major hallmarks of the pathogenesis of Alzheimer's disease (AD). Using monoclonal antibodies, different tau phosphoepitopes can be sensitively detected in the cerebrospinal fluid (CSF). A significant elevation in the levels of tau protein phosphorylated at threonine 231 (p-tau231) and threonine 181 (p-tau181) has been recently observed in CSF of AD patients (Hampel H et al., Arch Gen Psychiatry 2004 ; 61: 95-102 ; de Leon MJ et al., J Intern Med 2004 ; 256: 205-223). We analyzed a group of patients with a clinical diagnosis of AD, with possible AD, and nondemented controls. CSF levels of p-tau231 were measured using a specific antibody against the 231 tau phosphoepitope by Western blot (using an antibody provided by Peter Davies, New York, USA). CSF levels of p-tau181 were measured by ELISA (Innotest Phospho-Tau (181P), Innogenetics, Ghent, Belgium). CSF levels of p-tau231 and p-tau181 were significantly elevated in the patients with definite AD compared to the nondemented controls. Our preliminary results in a small group of cases with mild cognitive impairment (MCI) largely confirmed two earlier studies, which suggest that such an elevation may be a specific indicator of AD-related changes and could improve early detection and tracking disease progression. We conclude that p-tau231 and ptau181 in CSF represent a promising potential biological markers of AD.

dementia; Alzheimer's disease; early diagnosis; cerebrospinal fluid; phospho-tau proteins

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