Findings from the largest study to date of families with Alzheimer's Disease (AD) indicate that a gene, previously thought to account for up to half the cases of the disease occurring late in life, is associated primarily with a much smaller fraction of people - those in whom the disease develops under age 70.
"Since the majority of the approximately 4 million Americans who have AD become afflicted over the age of 70, the main genetic causes for the disease have yet to be identified," said NIMH grantee, Rudolph E. Tanzi, PhD, of Harvard's Massachusetts General Hospital, the senior author of the study. People with AD occurring under age 70 make up less than 10% of the AD population.
The gene under study, the Apolipoprotein E-4 (apoE-4) gene, appears in half to two-thirds of all Alzheimer's patient, compared to less than onethird of the general population, suggesting that it plays a significant role in the disease process. But the report shows that despite its prevalence, the gene is only a strong predictor of risk for the disease in individuals under 70, especially those who have inherited two copies of it - one from each parent - versus one copy.
The research is remarkable for its sample size of 679 individuals in 310 families, which was large enough for the researchers to separate out families by age at onset of AD symptoms.
For this study, families were recruited from memory disorder clinics, nursing homes, and the communities surrounding three sites (Massachusetts General Hospital, the University of Alabama School of Medicine in Birmingham, and the Johns Hopkins Medical School in Baltimore). They were required to contain at least two living blood relatives with memory problems. One member of the pair was required to meet standard criteria for probable AD, and the other for possible or probable AD. Autopsies, which are the only way to definitively diagnose AD, have been performed on 113 of the initial subjects, with 112 (99.1%) meeting neuropathologic criteria for definite AD.
Genetic research offers an opportunity to determine how AD develops and to develop a genetic test to identify individuals with the disease. Identification of persons with mild cognitive complaints who are at risk for AD would allow physicians to apply existing anti-dementia treatments before extensive brain damage develops, thereby slowing the progression of AD and substantially reducing the number of years of disability associated with the disease. This is especially important because no currently foreseeable treatment for AD would reverse permanent neuronal damage. Early detection strategies can provide reassurance to people whose age-related memory complaints are benign or help in the diagnosis of other more treatable causes of dementia. In addition, patients may wish to know their prognoses while their mental faculties are intact so that they can plan for their future care.