Iron and Alzheimer’s Disease: From Pathology to Imaging

Alzheimer’s disease (AD) is a debilitating brain disorder that afflicts millions worldwide with no effective treatment. Currently, AD progression has primarily been characterized by abnormal accumulations of β-amyloid within plaques and phosphorylated tau within neurofibrillary tangles, giving rise to neurodegeneration due to synaptic and neuronal loss. While β-amyloid and tau deposition are required for clinical diagnosis of AD, presence of such abnormalities does not tell the complete story, and the actual mechanisms behind neurodegeneration in AD progression are still not well understood. Support for abnormal iron accumulation playing a role in AD pathogenesis includes its presence in the early stages of the disease, its interactions with β-amyloid and tau, and the important role it plays in AD related inflammation. In this review, we present the existing evidence of pathological iron accumulation in the human AD brain, as well as discuss the imaging tools and peripheral measures available to characterize iron accumulation and dysregulation in AD, which may help in developing iron-based biomarkers or therapeutic targets for the disease.