A model for susceptibility polymorphisms for complex diseases: apolipoprotein E and Alzheimer disease

Area of Science:

• Neurogenetics
• Human Genetics
• Epidemiology

Background:

• Apolipoprotein E (APOE) polymorphisms are linked to Alzheimer's disease (AD) risk and age of onset.
• APOE genotyping differs from family-specific mutation analysis due to universal distribution and population variations.

Purpose of the Study:

• To explore the implications of APOE genotyping in understanding Alzheimer's disease pathogenesis.
• To highlight the paradigm shift from family-specific genetic counseling to epidemiological principles for common diseases.

Main Methods:

• Analysis of Apolipoprotein E (APOE) genotype data in relation to Alzheimer's disease (AD) risk and onset.
• Review of epidemiological principles for clinical genetic applications of common polymorphisms.

Main Results:

• APOE genotypes are universally distributed, with ethnic variations in allele frequencies, impacting AD risk.
• Current APOE genotyping cannot predict individual AD development or guarantee protection.
• Future discovery of additional susceptibility genes may enable widespread disease prediction.

Conclusions:

• The association of common polymorphisms like APOE with complex diseases like AD sets a precedent for genetic research.
• Anticipating the social, ethical, and legal challenges of widespread genetic prediction is crucial.
• The APOE-AD model serves as a template for studying other complex diseases and their implications.