Genetic testing for Alzheimer disease. Practical and ethical issues

Area of Science:

• Neurogenetics
• Molecular Biology
• Clinical Genetics

Background:

• Alzheimer disease (AD) genetics are complex, involving both rare mutations and common susceptibility polymorphisms.
• Understanding these genetic factors is crucial for improving diagnosis and management.

Purpose of the Study:

• To review the utility of genetic testing in Alzheimer disease diagnosis.
• To highlight the role of Apolipoprotein E (ApoE) genotyping in enhancing diagnostic specificity.

Main Methods:

• Analysis of genetic mutations in amyloid precursor protein, presenilin 1, and presenilin 2 genes.
• Evaluation of Apolipoprotein E (ApoE) genotyping in diagnostic strategies for AD.
• Review of collaborative studies on ApoE genotyping and diagnostic accuracy.

Main Results:

• Genetic testing for rare mutations is useful for early-onset AD, especially with family history.
• Apolipoprotein E (ApoE) epsilon 4 allele is a significant risk factor but does not predict onset age in healthy individuals.
• Sequential ApoE genotyping in diagnosis significantly increases specificity, with high positive predictive values (94-97%) in clinically diagnosed AD patients carrying the ApoE epsilon 4 allele.

Conclusions:

• Genetic testing, particularly ApoE genotyping, is a valuable tool for increasing the specificity of early Alzheimer disease diagnosis.
• Recommendations for the early use of ApoE genotyping in diagnostic protocols are provided.
• Ethical, social, legal, and actuarial considerations associated with genetic testing for AD must be addressed.