Abstract

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 onADrisk? We evaluate the effects of peripheral iron onADrisk 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 similar to 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 similar to 9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.

Authors	Lupton, Michelle K.; Benyamin, Beben; Proitsi, Petroula; Nyholt, Dale R.; Ferreira, Manuel A.; Montgomery, Grant W.; Heath, Andrew C.; Madden, Pamela A.; Medland, Sarah E.; Gordon, Scott D.; Lovestone, Simon; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Powell, John F.; Bush, Ashley I.; Wright, Margaret J.; Martin, Nicholas G.; Whitfield, John B.
Journal	JOURNAL OF ALZHEIMERS DISEASE
Pages	85-99
Volume	59
Date	1/01/2017
Grant ID	076113
Funding Body	Wellcome Trust
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.3233/JAD-170027