Genetic linkage analysis of nerve growth factor (beta) in familial alzheimer's 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 earlyonset FAD. Beta nerve growth factor (β‐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 β‐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 (θ < 0.03, z < −2.00) of late‐onset FAD with β‐NGF was excluded. Two apparent obligate crossovers between affected members were detected in different autopsy‐confirmed families. Based on these results, β‐NGF is not the gene responsible for late‐onset FAD in the families analyzed.