Nodular bilateral amygdala degeneration in demented individuals.

Among more than 2,050 brains in our Alzheimer disease brain banks, we came across three brains with well-demarcated indurated white-yellow nodules in the amygdalas. Microscopically, these nodules were composed of numerous lipid-laden macrophages located in the central region surrounded by an eosinophilic hyaline-like material with minimal reactive gliosis in the periphery. Neurons within these lesions had a normal appearance but were moderately decreased in number. Beta-amyloid, tau and alpha-synuclein immunostaining revealed no abnormal deposits within the nodules. The three patients had long histories of dementia (one linked to a presenilin-1 mutation). The neuropathological diagnoses were Alzheimer disease in two of them and an unclassified tauopathy with argyrophilic grains in the third. In conclusion, the pathogenesis of these lesions is uncertain. We favor that the degeneration has some relationship to the underlying dementing disease, either secondary to deafferentation or an alteration in metabolic demand, perhaps related to the bi-directional anatomical and functional connections that exist between the amygdala and the hippocampus or less likely as a primary event.