Variants in iron metabolism genes have been implicated in Alzheimer Disease (AD) pathogenesis.1 2 Previous studies suggested that the joint effect of haemochromatosis (HFE) C282Y (rs1800562) and transferrin (TF) C2 (P589S, rs1049296) variants increases the risk for AD.3–5 We sought to replicate this finding in a genetically homogeneous Midwestern Amish population. Our analysis of 706 Amish individuals (529 cognitively unimpaired (CU) and 177 with AD) found no significant association between these variants, individually or in combination, and AD risk. This result is consistent with another large-scale AD study also aiming to replicate the same findings.6
Iron overload has been implicated in AD pathogenesis through altered amyloid precursor protein processing and increased Aβ deposition.7 Both HFE and TF genes play a role in regulating iron metabolism, and variants of these genes may result in excessive iron in the…
