Alzheimer’s disease affects 4.5 million Americans, double those affected in 1980, and this figure is expected to grow to as many as 16 million by the year 2050 (Alzheimer’s Association 2006a). It accounts for the majority of dementias and is characterized by neuron loss in the brain, especially in the cortex and hippocampus, leading to progressive memory loss, degradation in cognition, and deterioration in language (Nussbaum and Ellis 2004). Generally, early onset of Alzheimer’s disease, prior to age 65 is rare, with the more prevalent late-onset form appearing on average at age 80 (Helmer, Joly, Letenneur, Commenges, and Dartigues 2001).

The early-onset forms of the disease that follow autosomal dominant inheritance are associated with one of three genes discovered in family linkage studies (studies of genes and markers that are located close to each other on chromosomes and tend to be transmitted through family lines), and DNA sequencing analysis (identification of base pairs in specific areas of DNA, often performed in persons affected with a given
health condition) (NHGRI n.d). These three genes are presinilin1 (PSEN1 on chromosome14), presenilin2 (PSEN2 on chromosome 1), and the gene associate with beta-amyloid precursor protein on chromosome 21 (Nussbaum and Ellis 2004). PSEN1 was found in over half of patients from affected families in a community study of early-onset Alzheimer’s Disease in France (Campion, Dumanchin, Hannequin, Dubois, Belliard, Puel, et al. 1999).

The vast majority of affected individuals are thought to have a combination of genetic and environmental factors (known as multifactorial inheritance) that causes the appearance of Alzheimer’s disease late in life. There have been some reports of attempts to detect Alzheimer’s disease before the affected person becomes incapacitated, and testing for mild cognitive impairment (MCI) has shown some promise because it separates those who have a greater likelihood of developing “clinically probable” Alzheimer’s from those with expected cognitive loss in normal aging (Petersen, Doody, Kurz, Mohs, Morris, Rabins, et al. 2001). Petersen and his colleagues describe Alzheimer’s disease as “clinically probable” because, at the present time, confirmation of the diagnosis requires autopsy examination of the brain for “plaques” and “tangles,” the hallmark abnormal structures associated with this condition (Alzheimer’s Association 2006b)

Perhaps as great a sadness for families who have a member affected with Alzheimer’s disease is the burden accepted by their caregivers. Over two-thirds of those affected live at home and the majority of these are cared for by family members (Alzheimer’s Association 2006a). The Alzheimer’s Association (http://www.alz.org) offers resources, education, and support for families and friends. The many community agencies who serve the elderly provide information about therapies, respite care, and counseling to assist in coping with the stresses of living with an affected person.

Mr. and Ms. P. (a fictional family) came to our Genetic Services Center requesting information and possible genetic testing for Alzheimer’s disease. Ms. P. was more worried than her husband and had been referred by a neurologist in the local community who suggested genetic counseling, especially for the couple’s children.

Mr. and Ms. P. related the history of their family (see Figure 27-1) on our first visit. Ms. P. and her husband (who is adopted and has no information about his family background) have 18-year-old twins, a boy and a girl, both healthy. Ms. P. is age 41, has no health problems, is a non-smoker, and works as an elementary school teacher.
Her husband is age 49 and was diagnosed with coronary artery disease in the last two months. He takes medication and exercises regularly, but occasionally smokes cigars. Mr. P. is the pastor of a large congregation in a local Protestant church. The P.’s refrain from alcohol and eat a “heart-healthy” diet.