Genetic linkage analysis of nerve growth factor (beta) in familial Alzheimer's disease.
Recent studies have not shown linkage of late-onset (mean age, greater than 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 BglII 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 (theta 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.
Alberts
M J
MJ
Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710.
Pericak-Vance
M A
MA
Royal
V
V
Bebout
J
J
Gaskell
P
P
Thomas
J
J
Hung
W Y
WY
Clark
C
C
Earl
N
N
Roses
A D
AD
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D003434:Crossing Over, Genetic / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D009414:Nerve Growth Factors