RNDr. Jan ?í?ný, CSc.
National Institute of Mental Health
Tau in Central Nervous System: neurotoxic and autoimmune component
Czech Science Foundation
Tau, natively soluble protein with minimal secondary structure can undergo pathological alteration, leading to tauopathies. The most prominent secondary tauopathy is Alzheimer disease (AD). It is assumed now that altered soluble tau species are the main vehicles of tau pathology. We will inject rats intracerebrally with various tau variants (full-length, truncacated, phosphorylated, oligomerized) and examine their effects on spatial learning and memory and on biochemical characteristics of cholinergic and glutamatergic neurotransmitter systems and identify forms critical for pathogenic influence. We will measure and compare the content of various forms of tau in cerebrospinal fluid of demented subjects and matched healthy controls to identify forms present specifically in diseased subjects. As altered tau forms could elicit antigenic response, which can further complicate pathology, we will measure and compare presence of antibodies against specific tau variants in bodily fluids of subjects with AD and matched healthy controls, with possible outcome of improved diagnosis of AD.