Tauopathies

The grounding supports abnormal tau gene mutation on chromosome 17 as one cause associated with pathological tau aggregation in some patients. It also supports tau misprocessing and post-translational modification, especially phosphorylation, as a pathogenic basis for tau accumulation. In Alzheimer disease, tau pathology is discussed alongside amyloid beta, but the supplied material does not establish amyloid beta as a general cause of tauopathies.

Tau normally stabilizes neuronal microtubules and contributes to neuronal structure and function. In tauopathies, tau undergoes abnormal modification and assembly into insoluble aggregates or amyloid fibrils, producing toxic gain of function, synaptic dysfunction, and neuronal death. The literature also describes propagation of tau aggregates between cells in a prion-like manner, with associated neuroinflammation, oxidative stress, and impaired synaptic plasticity.

Aging is supported as a factor associated with tauopathy progression and cognitive decline. The grounding also supports the presence of tau gene mutation in some affected patients as a disease-associated factor. Beyond this, the supplied material does not clearly establish additional general risk factors for tauopathies.

The supplied grounding does not provide a general standard-of-care treatment for tauopathies as a class. It does indicate that disease-modifying therapy targeting amyloid beta has been pursued in Alzheimer disease, and that tau is an increasing therapeutic target. However, no specific treatment modality or drug class is established here for tauopathies overall.