Tau is a naturally occurring protein found within the neurons of the brain. It is produced from a single gene known as MAPT (microtubule-associated protein tau). While present in various brain cells, its highest concentration is observed in the cerebral cortex. Tau proteins were first identified in 1975 as heat-stable proteins.
Normal Function of Tau
Tau proteins play a role in maintaining the internal framework of healthy brain cells. Their primary function involves stabilizing microtubules, which are structural components within neurons. These microtubules act like railroad tracks, guiding the transport of nutrients, signals, and other essential molecules throughout the cell.
Tau proteins interact directly with tubulin to promote the assembly of tubulin into microtubules and ensure their stability. This interaction supports structural integrity and efficient transport processes along axons. Tau’s ability to control microtubule stability is influenced by its different forms, known as isoforms, and by phosphorylation.
When Tau Goes Wrong
When tau undergoes abnormal changes, it can become dysfunctional. A key pathological change is hyperphosphorylation, where an excessive number of phosphate groups attach to the tau protein.
This hyperphosphorylation causes tau to detach from microtubules, disrupting their stability and the transport systems within neurons. Once detached, these tau proteins begin to misfold and clump together. They form insoluble aggregates known as neurofibrillary tangles, which are a hallmark of several neurodegenerative diseases.
These tangles accumulate inside neurons, interfering with normal cellular processes and communication between nerve cells. This can ultimately lead to neuronal dysfunction and the death of brain cells. The disruption of internal transport and cellular machinery due to tau aggregation contributes to the progression of neurodegenerative conditions.
Tau’s Role in Brain Diseases
Abnormal tau accumulation is a characteristic of a group of neurodegenerative disorders collectively known as tauopathies. Alzheimer’s disease is a key example where neurofibrillary tangles, composed of hyperphosphorylated tau, are a hallmark.
Other conditions linked to tau pathology include chronic traumatic encephalopathy (CTE), a progressive degenerative disease found in individuals with a history of repetitive brain trauma. Progressive supranuclear palsy (PSP) and certain forms of frontotemporal dementia (FTD) are also classified as tauopathies. The specific symptoms vary depending on where in the brain the tau aggregates accumulate and the particular type of tau involved, leading to diverse clinical presentations.