Description
Alzheimer’s disease (AD) describes a form of early-onset dementia involving a severe disease process of the cerebral cortex.
AD is still the leading cause of late-onset dementia. AD is mostly diagnosed on the basis of symptomatic changes and demographic features; therefore, biological markers which provide further insights are crucial. The human tau gene is positioned on chromosome 17 at position 17q21, spanning over 100 kb and consisting of 16 exons. Notably, exon 1 serves as the promoter and is transcribed but not translated. Tau protein is classified within the Microtubule-Associated Proteins (MAPs) group, known for their heat resistance and resilience to acid treatment without functional loss. There are six tau protein isoforms distinguished by the presence of three (3R) or four (4R) tubulin binding domains (repeats, R), each comprising 31 or 32 amino acids in the C-terminal region. Additionally, the N-terminal part of the molecule may contain one (1N), two (2N), or no inserts of 29 amino acids each. The variation in size, ranging from 352 to 441 amino acid residues, is linked to the inclusion or exclusion of sequences encoded by exons 2, 3, or 10. The post-translational modifications contribute to the generation of phosphorylated forms such as pTau217 and pTau181. In the case of pTau217, it refers to phosphorylation at residue 217 of the tau protein. Tau pathology in AD, where the usual job of the tau protein in organizing the cytoskeleton within axonal processes becomes ineffective because the protein loses its ability to bind to microtubules. This abnormal behavior is caused by changes in the shape and misfolding of tau’s usual structure, leading to its abnormal clumping into fibrillary structures inside the neurons of individuals with dementia. As a result, most of the changed tau protein in the disease is scattered and clumped in both the main body of the neuron and the isolated processes of affected neurons. Changes in the quantity or structure of tau protein can impact the stabilization of microtubules and other processes related to this protein. It’s worth noting that in AD patients, there are higher levels of phosphorylated tau 181 (pTau181) in the cerebrospinal fluid (CSF). Recent studies have highlighted increased levels of phosphorylated tau 217 (pTau217) in CSF, attracting significant attention because these levels rise before those of pTau181. This positions pTau217 as a promising and innovative biomarker in the realm of AD research.