Alzheimer disease (AD) is characterized by dementia that typically begins with subtle and poorly recognized failure of memory and slowly becomes more severe and, eventually, incapacitating. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations. Occasionally, seizures, Parkinsonian features, increased muscle tone, myoclonus, incontinence, and mutism occur. Death usually results from general inanition, malnutrition, and pneumonia. The typical clinical duration of the disease is eight to ten years, with a range from one to 25 years. Approximately 25% of all AD is familial (i.e., >/=2 persons in a family have AD) of which approximately 95% is late onset (age >60-65 years) and 5% is early onset (age <65 years).

Establishing the diagnosis of Alzheimer disease relies on clinical-neuropathologic assessment. Neuropathologic findings of beta-amyloid plaques and intraneuronal neurofibrillary tangles remain the gold standard for diagnosis. The clinical diagnosis of AD, based on signs of slowly progressive dementia and findings of gross cerebral cortical atrophy on neuroimaging, is correct approximately 80%-90% of the time. The association of the APOE e4 allele with AD is significant; however, APOE genotyping is neither fully specific nor sensitive. While APOE genotyping may have an adjunct role in the diagnosis of AD in symptomatic individuals, it appears to have little role at this time in predictive testing of asymptomatic individuals. Three forms of early-onset familial AD (EOFAD) caused by mutations in one of three genes (APP, PSEN1, PSEN2) are recognized. Molecular genetic testing of the three genes is available in clinical laboratories.

Because AD is genetically heterogeneous, genetic counseling of persons with AD and their family members must be tailored to the information available for that family. It should be pointed out that AD is common and that the overall lifetime risk for any individual of developing dementia is approximately 10%-12%. Genetic counseling for people with non-familial AD and their family members must be empiric and relatively nonspecific. First-degree relatives of a simplex case of AD (i.e., single occurrence in a family) have a cumulative lifetime risk of developing AD of approximately 15%-30%, which is typically reported as a 20%-25% risk. This risk is approximately 2.5 times that of the background risk (~27% vs 10.4%). In contrast, early-onset familial Alzheimer disease (EOFAD) is inherited in an autosomal dominant manner.