MAPT and argyrophilic grain disease: In normal human brain the ratio of 4R–3R tau is approximately one, whereas in many tauopathies, this ratio is altered; PSP, corticobasal degeneration (CBD), and argyrophilic grain disease all exhibit over-expression of 4R tau isoforms, whereas Pick’s disease is mainly characterized by tau inclusions rich in 3R tau isoforms (5–9).