Role of subcortical iron in Parkinson's disease, prodromal-depression, and dementia: Comparative links to anemias and osteoporosis.

Three reports employing Mendelian randomization and quantitative susceptibility mapping from 41,581-patients in the UK biobank provide evidence to support that excess subcortical iron accumulation causally accelerates Parkinson's disease (PD). While subcortical iron was not a significant driver of Alzheimer's disease (AD), neural shrinkage and ferroptosis in grey matter featured in vascular dementia. Subcortical iron was changed in depression, anemia and osteoporosis patients. Since iron chelators were not beneficial to either AD or PD patients in clinical trials, we propose that translational control of the iron-homeostatic protein α-synuclein (iron importer) could therapeutically normalize subcortical iron during PD progression.