Corpora amylacea and synaptic organization in the human brain analyzed by volume electron microscopy

The presence of corpora amylacea in the brain is a frequent finding in normal aging and in a broad spectrum of neurological disorders, yet the significance of these deposits for the organization of human cortical circuits remains unclear. Here, we combined complementary light and electron microscopy approaches to analyze temporal lobe epilepsy biopsy specimens with and without corpora amylacea. Samples containing corpora amylacea showed marked alterations in synaptic circuit microorganization, which were not restricted to areas of corpora amylacea accumulation but extended throughout the cortical tissue. These changes were characterized by neuronal loss, gliosis, reduced synaptic density, an increased proportion of inhibitory synapses, and larger synapses. Integration of these structural findings with clinical data from the same patients further supports the view that corpora amylacea are associated with disease-related pathological processes. Together, these findings provide a basis for understanding the potential significance of corpora amylacea in human brain circuit dysfunction and may help to inform future research studies focusing on disease mechanisms.