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Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.

Original publication

DOI

10.3233/jad-170027

Type

Journal article

Journal

Journal of Alzheimer's disease : JAD

Publication Date

03/07/2017

Volume

59

Pages

85 - 99

Addresses

QIMR Berghofer Medical Research Institute, Brisbane, Australia.

Keywords

GERAD1 Consortium, Alzheimer’s Disease Neuroimaging Initiative