Argyrophilic grain disease is a sporadic 4-repeat tauopathy

Takashi Togo, Naruhiko Sahara, Shu Hui Yen, Natalie Cookson, Takashi Ishizawa, Mike Hutton, Rohan De Silva, Andrew Lees, Dennis W. Dickson

Research output: Contribution to journalArticlepeer-review

218 Scopus citations


Argyrophilic grain disease (AGD) was first reported as an adult-onset dementia, but recent studies have emphasized personality change, emotional imbalance, and memory problems as clinical features of AGD. AGD is characterized by spindle- or comma-shaped argyrophilic grains in the neuropil of entorhinal cortex, hippocampus, and amygdala. Immunohistochemistry with monoclonal antibodies specific to tau isoforms with four (4R) or three (3R) repeats in the microtubule binding domain showed immunostaining of grains with 4R, but not 3R, tau antibodies, suggesting that AGD was a 4R tauopathy. The tau isoform composition of AGD was confirmed with densitometric analysis of Western blots of sarkosylinsoluble tau from the medial temporal lobe of AGD brains with a range of concurrent neurofibrillary pathology and compared with Alzheimer controls. The 4R/3R ratio was 1 or less for Alzheimer disease; the 4R/3R ratio was more than 1 for AGD, decreasing with increasing neurofibrillary pathology and demonstrating that insoluble tau in AGD was enriched in 4R tau. The frequency of the extended tau haplotype was not different in AGD compared to other sporadic 4R tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Furthermore, AGD occurred in PSP and CBD more frequently than in dementia controls, including Alzheimer disease. These results suggest that AGD, PSP and CBD are 4R tauopathies that share common pathologic, biochemical, and genetic characteristics.

Original languageEnglish (US)
Pages (from-to)547-556
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
StatePublished - 2002


  • Alzheimer disease
  • Argyrophilic grain disease
  • Corricobasal degeneration
  • Progressive supranuclear palsy
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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