Microtubule-associated protein tau 4-repeat isoform fibrillar aggregates (4R Tau aggregates)

Microtubule-associated protein tau 4-repeat (4R) isoform fibrillar aggregates are pathological protein assemblies composed of tau protein containing four microtubule-binding repeat domains (MTBR). In a healthy state, tau stabilizes microtubules and facilitates axonal transport, but in certain neurodegenerative conditions, it undergoes hyperphosphorylation and misfolds into insoluble filaments (NIH, 2020). These 4R-specific aggregates are the defining pathological feature of 4R tauopathies, such as Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), distinguishing them from Alzheimer's disease which contains both 3R and 4R isoforms (Alzforum, 2024). Therapeutic interventions targeting these aggregates aim to halt disease progression by clearing extracellular tau 'seeds' using monoclonal antibodies or by inhibiting the aggregation process itself (BioSpace, 2026). Additionally, specialized PET tracers like PI-2620 are being developed to selectively bind these 4R filaments for improved diagnostic accuracy and monitoring of clinical trial outcomes (NIH, 2024).

Other names

4R tau4-repeat tauopathy aggregatesMAPT 4R aggregates4-repeat tau filaments

Passive immunotherapy to clear extracellular tau seeds, inhibition of tau aggregation, and reduction of tau protein expression via antisense oligonucleotides (ASOs) or siRNA (NIH, 2020; BioSpace, 2026).