title: Co-occurrence of argyrophilic grain disease in sporadic amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Phosphorylated TDP-43 (pTDP-43) is the pathological protein responsible for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Recently, it has been reported that accumulation of pTDP-43 can occur in the brains of patients with argyrophilic grain disease (AGD), in which phosphorylated 4-repeat tau is the pathological protein. To elucidate the association of ALS with AGD, we examined the brains from 37 consecutively autopsied patients with sporadic ALS (age range 45-84 years, mean 71.5 ± 9.0 years).
  
  
  METHODS
  Sections from the frontotemporal lobe were stained with the Gallyas-Braak method and also immunostained with antibodies against phosphorylated tau, 4-repeat tau and pTDP-43.
  
  
  RESULTS
  Fourteen (38%) of the 37 ALS patients were found to have AGD. With regard to staging, 5 of these 14 cases were rated as I, 4 as II and 5 as III. pTDP-43 immunohistochemistry revealed the presence of positive neuronal and glial cytoplasmic inclusions in the affected medial temporal lobe in many cases (93% and 64%, respectively). On the other hand, pTDP-43-positive small structures corresponding to argyrophilic grains were observed only in one case. A significant correlation was found between AGD and the Braak stage for neurofibrillary pathology (stage range 0-V, mean 2.1). However, there were no significant correlations between AGD and any other clinicopathological features, including dementia.
  
  
  CONCLUSIONS
  The present findings suggest that co-occurrence of AGD in ALS is not uncommon, and in fact comparable with that in a number of diseases belonging to the tauopathies or α-synucleinopathies.
authors.affiliation: Department of Pathology, Center for Bioresources, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Soma
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Fu
authors.forename: K
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: O
authors.initials: O
authors.lastname: Onodera
authors.forename: A
authors.initials: A
authors.lastname: Kakita
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology; D008297:Male; D008875:Middle Aged; D024801:Tauopathies / Q000150:complications* / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016875:tau Proteins