Iron in the Ageing Brain

Iron as an essential trace element is a major contributor to many metabolic pathways in the body and the brain. The transfer of iron through the blood-brain barrier and the distribution and storage in the brain is tightly regulated in order to prevent neurotoxicity. Increased iron levels in the ageing brain in cortex and basal ganglia lead to impaired cognitive and motor functions. Moreover, iron contributes to neurodegenerative diseases in the elderly such as Parkinson's and Alzheimer's disease. Increased iron deposition in Parkinson's disease can be found in the substantia nigra where substantial neuronal loss occurs. Iron also promotes aggregation of a-synuclein in Lewy bodies and production of toxic hydroxyl radicals. In Alzheimer's disease, iron participates in the generation of beta-amyloid plaques and neurofibrillary tangles. Vice versa, reduced ferroxidase activity of the amyloid precursor protein contributes to increased cerebral iron accumulation. Ferritin levels in the cerebrospinal fluid (CSF) are increased in patients with the APOE4 allele, a risk factor for Alzheimer's disease. Clinically, iron levels of the basal ganglia and the hippocampi are negatively associated with cognitive performances. Furthermore, increased CSF ferritin levels are associated with earlier disease onset. Last but not least, the pathological cerebral iron accumulation in the group of disorders called neurodegeneration with brain iron accumulation (NBIA) emphasizes the important role of iron in neurodegenerative diseases.