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Using Molecular Probes In The Study Of Alzheimer's Disease

F. Marott Sinex, PhD, is chief of the Section on Bio-Medical Gerontology, Boston University School of Medicine, Boston, Massachusetts and president of the Eastern Massachusetts Alzheimer's Disease and Related Disorders Association. disease. In this article, I will be discussing how such probes may be used in diagnosis and in the study of inheritance. Specifically, I will discuss a particular approach, using a probe to measure the number of copies of a gene which are present in a quantitative manner. Schweber et all and Delabar et al2 have tested the hypothesis that there is a tripling of a segment of chromosome 21 in Alzheimer's disease. 1,2 Schweber has refined the method so that it is applicable to individual patients. For the purposes of this discussion I will divide the general population into different categories based on the premise that a chromosomal defect associated with Alzheimer's disease is present. There are people who are free of any genetic propensity, the normals, and there are others who carry a demonstrable abnormality. The latter differ in the probability that the disease will be expressed in their lifetime. Penetrance in those carrying the abnormality approaches 100 percent in a small percentage of families. In some of these families the disease occurs early, often before the age of 65. In most families the disease occurs later in life and in those who have the propensity only onethird may express the disease during their lifetime.3'4 In such families, Alzheimer's disease is not an overwhelming consideration, but a concern like a family history of heart disease, cancer or stroke. As suggested by the name, the origins of sporadic disease are obscure. They may be genetic, with sporadic penetrance, or originate from extreme age, viral, or environmental causes. In a genetic sense, spontaneous