Argyrophilic grain disease: a clinicopathological review of an overlooked tauopathy

Argyrophilic grain disease (AGD) is a sporadic tauopathy and actually the second most frequent cause of dementia after Alzheimer’s disease. Patients can present with slowly progressive cognitive decline as well as psychiatric manifestations such as depression. Definite diagnosis of AGD can only be made by post-mortem examination of the brain. Neuropathological features include argyrophilic grains in limbic areas along with oligodendroglial coiled bodies in hippocampal and amygdaloid white matter, and ballooned neurons in the amygdala. AGD, however, can often be overlooked and missed on neuropathologic examination as there are actually no specific clinical manifestations that would be considered highly suggestive of AGD. Thus, it is not uncommon to find neuropathological features of AGD in patients who do not present with any apparent neurological manifestations. The aim of this review is to provide an overview of what is currently known about AGD as well as raise its awareness among both neurologists and neuropathologists who may otherwise overlook this interesting tauopathy. We believe that patients above the age of 60 years should undergo post-mortem screening for AGD to avoid missed opportunity for diagnosis and enable future clinicopathological studies.