Genetic testing for Alzheimer disease. Practical and ethical issues
A. D. Roses
Center for Human Genetics, Duke University Medical Center, Durham, NC, USA.
The dissection of the heterogeneous genetics of the Alzheimer diseases
(ADs) is currently more advanced than in any other common disease. Not only
are 3 uncommon autosomal dominant mutation loci identified, but universally
inherited susceptibility polymorphisms associated with risk and age of
onset distributions for familial and "sporadic" AD are also confirmed. The
utility of testing for mutations of the amyloid precursor protein and the
presenilin 1 and presenilin 2 genes conforms to strategies in common use
for rare mutations. The selection of patients with very early-onset AD,
especially those with family histories of the disease, will increase the
possibility of diagnosis. All testing should be performed using recommended
counseling procedures. Apolipoprotein E (ApoE) susceptibility polymorphisms
are genetic risk factors but do not allow prediction of the age of onset of
AD for cognitively normal individuals. Recent large, collaborative studies
have found that when ApoE genotyping is used sequentially in diagnosis
following criteria-based evaluations, the specificity of early diagnosis is
significantly increased. For patients clinically diagnosed with AD who
carried an ApoE epsilon 4 allele, the positive predictive value was 94% and
97% in 2 multicenter collaborative series. The utility of ApoE genotyping
is reviewed and recommendations for early use in diagnosis are explained.
There are ethical, social, actuarial, and legal problems currently
associated with genetic testing and these concerns are also discussed.
