Co-occurrence of argyrophilic grain disease in sporadic amyotrophic lateral sclerosis

K. Soma, Y.‐J. Fu, K. Wakabayashi, O. Onodera, A. Kakita and H. Takahashi (2012) Neuropathology and Applied Neurobiology38, 54–60 Co‐occurrence of argyrophilic grain disease in sporadic amyotrophic lateral sclerosis Aims: 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.