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PL‐05‐03: Apolipoprotein E as a therapeutic target for Alzheimer's disease
Author(s) -
Mahley Robert W.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.568
Subject(s) - neuropathology , apolipoprotein e , neuroscience , alzheimer's disease , oxidative stress , biology , disease , medicine , biochemistry
Background: Understanding the pathway to common Alzheimer’s disease (AD) remains our ultimate challenge. Research has given us some pieces of this puzzle but there are still too many gaps in our knowledge. We recognise that identifying susceptibility genes will fill many of these by pinpointing primary causal components in the pathway to disease. However, the last fifteen years of genetic research has succeeded in identifying only one definite susceptibility gene for common AD, namely Apolipoprotein E4. However, this gene famine is about to end. Over the next few years large scale genome-wide studies (GWAS) will identify several new susceptibility genes with compelling levels of evidence. Methods: Current GWA studies in AD will be reviewed and a new powerful GWAS described, which includes over 20,000 case/control samples from UK, Europe and the USA. The GWAS is designed in two stages. The first comprises a discovery phase involving over 4,000 AD cases and 9,000 controls genotyped on Illumina platforms, typing an average of 500,000 single nucleotide polymorphisms per person. The second stage seeks to extend the first by genotyping the it’s top hits in independent samples comprising 3,000 AD cases and 4,000 controls. Results: At least two new susceptibility genes for AD are confirmed in this study showing genome-wide significance in the discovery phase and extended evidence in independent samples (p< 1310 ). Moreover, these data show strong evidence suggesting further susceptibility loci for AD. Conclusions: New susceptibility genes have been confirmed and their putative functional roles in the disease pathway will be discussed. These findings also support the necessity for even more powerful GWA studies to identify further novel susceptibility genes.