AUTHOR=Xu He , Finkelstein David I. , Adlard Paul A. TITLE=Interactions of metals and Apolipoprotein E in Alzheimer’s disease JOURNAL=Frontiers in Aging Neuroscience VOLUME=6 YEAR=2014 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2014.00121 DOI=10.3389/fnagi.2014.00121 ISSN=1663-4365 ABSTRACT=

Alzheimer’s disease (AD) is the most common form of dementia, which is characterized by the neuropathological accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs). Clinically, patients will endure a gradual erosion of memory and other higher order cognitive functions. Whilst the underlying etiology of the disease remains to be definitively identified, a body of work has developed over the last two decades demonstrating that AD plasma/serum and brain are characterized by a dyshomeostasis in a number of metal ions. Furthermore, these metals (such as zinc, copper and iron) play roles in the regulation of the levels of AD-related proteins, including the amyloid precursor protein (APP) and tau. It is becoming apparent that metals also interact with other proteins, including apolipoprotein E (ApoE). The Apolipoprotein E gene (APOE) is critically associated with AD, with APOE4 representing the strongest genetic risk factor for the development of late-onset AD. In this review we will summarize the evidence supporting a role for metals in the function of ApoE and its consequent role in the pathogenesis of AD.