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.