GENETIC-LINKAGE ANALYSIS OF NERVE GROWTH-FACTOR (BETA) IN FAMILIAL ALZHEIMERS-DISEASE

Recent studies have not shown linkage of late-onset (mean age, > 60 years) familial Alzheimer's disease (FAD) to the chromosome 21 locus reported linked to early-onset FAD. Beta nerve growth factor (beta-NGF) has been considered a candidate gene in the pathogenesis and therapy of FAD, based on its localization in the cortex and hippocampus and its ability to enhance the growth and survival of cholinergic neurons. A 1.5-kb fragment of the beta-NGF gene was used to detect a Bgl II restriction fragment length polymorphism, which was then used for linkage analysis. A total of 30 families (27 late onset) with 147 affected members were studied. Close linkage (0 less-than-or-equal-to 0.03, z less-than-or-equal-to -2.00) of late-onset FAD with beta-NGF was excluded. Two apparent obligate crossovers between affected members were detected in different autopsy-confirmed families. Based on these results, beta-NGF is not the gene responsible for late-onset FAD in the families analyzed.