Tuesday, January 15, 2013

Fat Gene (FTO) Linked to Alzheimer's Disease Risk

The relationship between obesity and risk for Alzheimer's disease is a controversial area of research.

Several studies have found a prospective increase in risk for Alzheimer's disease in those with obesity.  However, the association has been inconsistent.  Some studies have even found a reduced risk of later Alzheimer's disease in overweight populations.

One method to further investigate the possible obesity-Alzheimer's risk association is through direct genetic studies of genes known to be related to obesity.

Christiane Reitz and colleagues from the U.S. National Institute on Aging recently published this type of study in the journal PLOS One.

They focused on polymorphisms of the Fat and Obesity-Associated (FTO) gene.  The FTO gene is located on the q arm of human chromosome 15.  Polymorphisms associated with FTO intron 1, intron 2 and exon 2 have been linked to increased rates for obesity and also have some evidence of being linked to risk for Alzheimer's disease.

To study this issue in more detail, Reitz and colleagues conducted a single nucleotide protein (SNP) analysis of the FTO gene in Alzheimer's disease subjects and controls.  Two independent samples with a combined sample size approaching 3000 subjects were used in the SNP analysis. Additionally, they conducted a FTO gene expression analysis of Alzheimer's disease cases that had been confirmed by brain neuropathological analysis. 

The key finds from this genetic study were:
  • Eight FTO SNP regions were linked to variation in risk for Alzheimer's disease
  • Eleven FTO haplotypes were identified that significantly contributed to risk for Alzheimers's disease
  • Gene expression studies in brain tissue of Alzheimer's disease subjects showed lower FTO gene expression compared to controls
The authors note their study findings "confirm the association between genetic variation in Intron 1, Exon 2 or Intron 2 in the FTO gene and AD".  (AD=Alzheimer's disease).

They propose several mechanisms for this association.  FTO gene status increases risk for hyperinsulinemia and type II diabetes, known risk factors for Alzheimer's disease.  They note a second potential mechanism where FTO gene status contributes to Alzheimer's disease by a vascular pathology (i.e. hypertension, lipid dysregulation, atherosclerosis).  Finally, they note obesity increases inflammatory markers by increasing adipokines and cytokines that may contribute to risk or severity of Alzheimer's disease.

This is an important study in the ongoing search to understand the effect of obesity on Alzheimer's disease risk.  Exploring genetic mechanisms is a promising approach to complement  epidemiological risk factor studies to advance our understanding of Alzheimer's disease. 

Photo of willet from the author's files. 

Reitz C, Tosto G, Mayeux R, Luchsinger JA, & the NIA-LOAD/NCRAD Family Study Group and the Alzheimer's Disease Neuroimaging Initiative (2012). Genetic Variants in the Fat and Obesity Associated (FTO) Gene and Risk of Alzheimer's Disease. PloS one, 7 (12) PMID: 23251365

1 comment:

  1. Millions of people across the world are experiencing Alzheimer’s disease and it’s been nice to have read this article.

    Alzheimer’s clinic Toronto