Tau pathology in Alzheimer´s - understanding pathophysiology through biomarkers in blood and CSF

Tau pathology is key in Alzheimer´s disease (AD), and plasma pTau shows great promise as easily accessible blood biomarkers.

This project builds on generating further knowledge on tau pathophysiology, and specifically aim to:study the association between pTau fragments that shows increased secretion from neurons (e.g. pTau181) and the C-terminally extended tau species tau368 that shows a relative decrease due to deposition in tau aggregates;understand which pTau peptides that shows the earliest change in AD, and tightest association with tau pathology, when analyzed simultaneously by mass spectrometry;explore which tau variants are found in secreted tau oligomers, which are believed to foster spreading of tau pathology in the AD brain;develop and evaluate a novel method for brain-derived tau in plasma that could serve as a neurodegeneration biomarkermake an assay for peripheral “big tau” to learn on how much of plasma tau is derived from CNS and peripheral neurons, respectively, an if big tau can serve as a biomarker for peripheral neuronal damage;study the physiology of pTau fragments in hibernating animals, which are unique models for brain tau phosphorylation      We believe this project will make the route towards clinically useful blood biomarkers shorter, and allow for a Personalized Medicine characterization of patients, which will be of importance for all of clinical management of individuals at risk of AD and also drug development.