Different phosphorylated tau isoforms in biochemical diagnosis of Alzheimer’s disease

Abstract Background In the context of Alzheimer's disease (AD), blood‐based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD. Measuring levels of different phosphorylated tau in the blood can provide insights into the extent of tau pathology in the brain. Phosphorylated tau (pTau) serves as a blood biomarker signaling the existence of AD‐related alterations, with pTau217, pTau181, and pTau231 proving to be significant indicators in this context. The primary goal of this study is to investigate the diagnostic utility of measuring plasma pTau217, pTau181 and pTau231 levels in identifying possible AD cases. This study intends to evaluate how effectively the concentrations of pTau217, pTau181 and pTau231 in the blood can differentiate individuals with CSF biomarker‐confirmed AD in comparison to CSF biomarker‐negative control group. Method Plasma concentrations of pTau217, pTau181 and pTau231 were measured by in‐house Single molecule array (Simoa) assays developed at the University of Gothenburg (UGOT p‐tau217, pTau181 and pTau231). The quantitative assessment of classical biomarkers (Aβ‐42, Aβ‐42/Aβ‐40, tTau, and pTau181) in the CSF of patients with possible AD according to the Erlangen Score algorithm (ER 2 and 3) and controls (ER 0) were performed by Lumipulse. Result Significantly The levels of pTau217, pTau181 and pTau231 correlated positively with CSF tTau, pTau181 and negatively with CSF Aβ1‐42 and Aβ ratio. The greatest effect size was observed for pTau217 (d=1.63), moderate for pTau181 (d=0.57) and pTau231 (d=0.3) respectively. Conclusion The results of the present study indicate that plasma pTau217 could be the most valuable blood biomarker for AD diagnosis among the tested isoforms.