The neuropathology of neurodegeneration with brain iron accumulation

Neuropathology plays a key role in characterizing the pathogenesis of neurodegenerative diseases including forms of neurodegeneration with brain iron accumulation (NBIA). Despite important differences, several genetically diverse forms of NBIA nevertheless share common features in addition to iron deposition, such as the presence of neuroaxonal spheroids. Multiple forms of NBIA also demonstrate tau or synuclein pathology, suggesting parallels with both Alzheimer and Parkinson diseases. This chapter summarizes what has been learned from the study of human patient tissues. Gross and microscopic findings are delineated, and similarities and differences between forms of NBIA are presented. Neuropathologic findings often help characterize fundamental features of disease and provide a springboard for more focused hypothesis-driven studies. Lessons learned from neuropathology thus contribute much to the characterization of the molecular mechanisms of disease.