Neuropathological Asymmetry in Argyrophilic Grain Disease

Abstract

The presence of argyrophilic grains in the neuropil is associated with a form of dementia. We investigated morphological asymmetry in 653 consecutive autopsy patients from a general geriatric hospital (age [mean +/- SD] = 81.1 +/- 8.9 years), focusing on those from patients with advanced argyrophilic grain disease. Paraffin sections of the bilateral posterior hippocampi were immunostained with anti-phosphorylated tau and anti-4-repeat tau antibodies and by the Gallyas-Braak method. In a side-to-side comparison, asymmetry was defined when either the extent or the density of argyrophilic grains was different. Of the 653 subjects, 65 (10%) had Stage 3 argyrophilic grain disease, and 59 (90.8%) showed histopathological asymmetry. Antemortem computed tomographic images (n = 24), magnetic resonance imaging scans (n = 8), and combined computed tomographic and magnetic resonance images (n = 15) were available; images from 20 of the 47 subjects showed asymmetry that correlated with the histopathological asymmetry. Cerebral cortical asymmetry consistent with the histopathology was also visible in N-isopropyl-123I-p-iodoamphetamine single photon emission computed tomographic images from 6 patients and 18F-labeled fluorodeoxyglucose positron emission tomographic images from 2 patients. Thus, asymmetric involvement of the medial temporal lobe in patients with advanced argyrophilic grain disease may represent a diagnostic feature and contribute to distinguishing dementia with grains from Alzheimer disease.