NameFe65
OrganismHomo sapiens
Aging PhenotypeN/A
Allele TypeN/A
StrainN/A
DescriptionA large epidemiological study of sporadic dementia of the Alzheimer`s type (DAT) indicated that having at least one copy of the minor allele was associated with a decreased risk for DAT (Hu et al, 1998). The Fe65 protein binds to the intracellular domain of the beta-amyloid precursor protein and may modulate the internalization of betaPP. The deletion/substitution of the minor allele occurs within the intron that interrupts the two exons encoding the betaPP binding site. Linkage of the minor allele with resistance to DAT was confirmed by Lambert et al. (2000) in populations over 75 years-of-age, while epidemiological studies that did not support the linkage (Prince et al., 2001; Guenette et. al, 2000; and Papassotiropoulos et al, 2000) lacked representation of subjects older than 75 years-old. These results suggest that any protective effect the minor allele of Fe65 might have is restricted to individuals older than 75 years.
Gene FunctionAmyloid Beta A4 Precursor Protein-Binding, Family B, Member 1. The Fe65 protein binds to the intracellular domain of the beta-amyloid precursor protein and may modulate the internalization of betaPP.
Other PhenotypesThe human Fe65 mRNA, cloned from a fetal brain cDNA library, encodes a protein of 735 amino acids. Using fluorescence in situ hybridization the gene was mapped to human metaphase chromosome band 11p15. The gene contains 14 exons; the 5-flanking region is TATA-less and GC-rich with at least five putative Sp1 binding sites. A trinucleotide deletion and single base pair substitution within intron 13 produces a minor allele.
HomologsC.e. FEH-1, Y110A2AL.13
R.n. APBB1, APBB3
M.m. APBB1, APBB2
H.s. APBB2, FE65L2
Primary ReferenceBressler, S. L., Gray, M. D., Sopher, B. L., Hu, Q., Hearn, M. G., Pham, D. G., Dinulos, M. B., Fukuchi, K., Sisodia, S. S., Miller, M. A., Disteche, C. M., and Martin, G. M. (1996). cDNA cloning and chromosome mapping of the human Fe65 gene: interaction [Abstract]
Other ReferencesHu, Q., Kukull, W. A., Bressler, S. L., Gray, M. D., Cam, J. A., Larson, E. B., Martin, G. M., and Deeb, S. S. (1998). The human FE65 gene: genomic structure and an intronic biallelic polymorphism associated with sporadic dementia of the Alzheimer type. H [Abstract]
Lambert, J. C., Mann, D., Goumidi, L., Harris, J., Pasquier, F., Frigard, B., Cottel, D., Lendon, C., Iwatsubo, T., Amouyel, P., and Lambert, J. C., Mann, D., Goumidi, L., Harris, J., Pasquier, F., Frigard, B., Cottel, D., Lendon, C., Iwatsubo, T., Amouye [Abstract]
Prince, J. A., Feuk, L., Sawyer, S. L., Gottfries, J., Ricksten, A., Nagga, K., Bogdanovic, N., Blennow, K., and Brookes, A. J. (2001). Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate gene [Abstract]
Guenette, S. Y., Bertram, L., Crystal, A., Bakondi, B., Hyman, B. T., Rebeck, G. W., Tanzi, R. E., and Blacker, D. (2000). Evidence against association of the FE65 gene (APBB1) intron 13 polymorphism in Alzheimer's patients. Neurosci Lett 296, 17-20. [Abstract]
Papassotiropoulos, A., Bagli, M., Becker, K., Jessen, F., Maier, W., Rao, M. L., Ludwig, M., and Heun, R. (2000). No association between an intronic biallelic polymorphism of the FE65 gene and Alzheimer's disease. Int J Mol Med 6, 587-9. [Abstract]
Relevant LinksHumanPD: http://www.proteome.com/databases/HumanPD/reports/APBB1.html
LocusLink: http://www.ncbi.nih.gov/LocusLink/LocRpt.cgi?l=322
KeywordsAlzheimer disease, H. sapiens, human, neuron, neurodegeneration, dementia, betaPP