CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies

Abstract

Tau and beta-amyloid (1-42) (Abeta42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Abeta42 and phospho-tau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Abeta42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782 +/- 0.048 (mean +/- SE) for tau and to 0.839 +/- 0.042 for phospho-tau (p = 0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB.

Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with Alzheimer's disease and other dementias: preliminary findings

“…In the present study CSF levels of phosphotau were increased in AD patients when compared to normal controls from the literature and to patients with OD, a finding that is similar to previous reports 11,20,21,23,24 . However, It is important to reinforce that phosphotau levels in a normal range do not exclude AD.…”

“…To solve this overlap, a group of investigators 19 developed a method able to detect hyperphosphorylated tau (phosphotau) and obtained elevated levels when comparing AD patients to controls. Other studies reproduced these results, suggesting that phosphotau is a more specific biomarker then total tau for AD diagnosis 20,21 . The abnormal phosphorylation of tau protein is an early event in AD pathophysiology and is restricted to cerebral regions affected by the disease.…”

“…Until now, different immunoassays were developed directed to different phosphosites as serine 199, threonine 231, serine 396/404, threonine 231/serine 235 and threonine 181 21,23 . Vanmechelen et al 24 developed an ELISA assay specific for the phosphorylation site proline-directed to Thr 181.…”

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…CSF P-tau level specifically increase in AD patients compared with those with FTD, vascular dementia or control subjects (Hampel, Buerger et al 2004). Regarding DLB, results are more conflicting with studies describing increase of P-tau CSF levels and others reporting normal concentrations (Vanmechelen, Vanderstichele et al 2000;Parnetti, Lanari et al 2001). So, an increase in P-tau CSF levels is observed in AD and MCI patients (Itoh, Arai et al 2001;Andreasen, Vanmechelen et al 2003;Herukka, Hallikainen et al 2005).…”

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

“…Normal CSF levels of P-tau are found in psychiatric disorders such as depression, 14,96 in chronic neurological disorders such as amyotrophic lateral sclerosis and PD, 14,52,70 and also in other most cases with other dementia disorders such as VAD, FTD, and LBD. 21,52,70,71,86,92,93 Furthermore, although there is a very marked increase in CSF T-tau in CJD, most patients with CJD have normal or only mildly elevated CSF P-tau. 26 In a large set of patients with CJD cases and other dementias, the ratio of P-tau to T-tau in CSF was found to discriminate CJD from other neurodegenerative disorders without any overlap.…”