Ratio Aβ1-42:p-Tau: a Possible Diagnostic Tool in Differentiating Dementias

Abstract

Background: Patients with Alzheimer's disease (AD) present a typical biochemical profile of biomarkers: low concentration of β amyloid 1-42 (Aβ1-42), high concentration of total Tau (t-Tau) and phosphorylated Tau at threonine 181 (p-Tau). Several neurodegenerative diseases may overlap with AD, both in regards to clinical symptoms and neuropathology. Many data suggest that Alzheimer's disease (AD) pathophysiology can be identified using biomarkers. It has been hypothesized that subjects with dementia due to AD showed low levels of Aβ1-42 combined with the highest levels of total Tau and phosphorylated Tau; moreover, it has been hypothesized that the ratio Aβ1-42:p-Tau further help in discriminating Alzheimer's disease from other diagnoses. The aim of this work is to verify this hypothesis in our cohort of patients and to investigate if the same ratio could be a sensitive index able to discriminate MCI due to neurodegenerative factors (MCId) from MCI due to vascular factors (MCIv).

Methods: Two hundred sixty-two patients meeting the NIA-AA and NINDS-AIREN criteria were diagnosed as follow: AD in 120 patients [mean age 71.6 (42 - 87)], FTD in 23 patients [mean age 67.3 (46 - 78)], LBD in 17 patients [mean age 73.2 (58 - 83)], VAD in 9 patients [mean age 71.2 (60 - 81)]. According to the criteria proposed by Petersen RC, 24 patients had the diagnosis of MCId [mean age 71.8 (59 - 81)], 38 MCIv [mean age 69.3 (55-82). The comparison between the ratio of Aβ1-42/p-Tau among the six groups was done using t-test for independent samples. A p-value < 0.05 was considered to represent statistical significance. The ROC (Receiver Operating Characteristic) curve analysis was made using R-studio software.

Results: The ratio Aβ1-42:p-Tau was significantly lower in AD and MCId with respect to all the other groups and the difference was also statistically significant between MCId and MCIv.

Conclusions: Aβ1-42:p-Tau ratio has potential for being implemented in the clinical routine for differential diagnosis between AD and other dementias and to distinguish underling pathology such as neurodegenerative or vascular disease.