Argyrophilic grain disease (AGD),
a 4R tauopathy
Rev Neurol (Paris). 2002 Feb;158(2):155-65. Review. French.
PMID: 11965171 [PubMed - indexed for MEDLINE]
CA, Sergeant N, Schraen-Maschke S, Lebert F,
Ruchoux MM, Sablonniere B, Pasquier F, Delacourte
A. Diffuse form of argyrophilic grain disease:
a new variant of four-repeat tauopathy different
from limbic argyrophilic grain disease.
Markus Tolnay · Nicolas Sergeant · Antoine Ghestem · Sonia Chalbot · Rob A. I. deVos · Ernst N. H. Jansen Steur ·Alphonse Probst · André Delacourte
Argyrophilic grain disease and Alzheimer’s disease are distinguished
by their different distribution of tau protein isoforms
Acta Neuropathol (2002) 104 :425–434
neuronal and glial tau filamentous inclusions are
hallmarks of neurodegenerative tauopathies, among
them Alzheimer’s disease (AD), progressive
supranuclear palsy (PSP), corticobasal degeneration
(CBD), Pick’s disease (PiD), and argyrophilic
grain disease (AgD). AgD is a late onset dementia
in which pathologically aggregated tau proteins are
found in limbic structures in the shape of distinct
argyrophilic grains and coiled bodies.
Until now tau protein deposits in AgD have not been assessed biochemically. We therefore decided to investigate the electrophoretic profile of pathological tau protein as well as the tau protein isoform composition of filamentous inclusions in AgD cases. A distinct pathological tau doublet at 64 and 69 kDa and a minor 74-kDa band was obtained in two AgD cases with only very mild concomitant AD pathology (Braak stage I), while in two AgD cases with moderate AD pathology (Braak stage II and III, respectively), an additional minor band at 60 kDa was detected. Thus, the pathological tau profile (PTP) in pure AgD cases differs from both the PTPs in AD (tau triplet at 60, 64 and 69 kDa, minor band at 74 kDa) and PiD (major tau doublet at 60 and 64 kDa, minor band at 69 kDa) but not from those in PSP and CBD. Using a two-dimensional gel electrophoresis approach anti-exon 10 antiserum strongly stained the AgD doublet and the minor 74-kDa band, while anti-exon 2 and 3 antisera only faintly stained the 69- and the minor 74-kDa component, thus suggesting that pathological tau aggregates in AgD are mainly made of four-repeat (4R) tau isoforms. Furthermore, in contrast to earlier immunohistochemical studies, we now show biochemically that Ser262 indeed is phosphorylated in the PTP of AgD. Finally, expression of normal tau protein was not found to be altered in AgD. Altogether, our results demonstrate that AgD is characterized by a major tau doublet that is distinct from AD and PiD. AgD, however, shares the pathological tau doublet (64 and 69 kDa) as well as the predominance of 4R tau isoforms with CBD and PSP.