Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.

Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.

[1]  P Brown,et al.  Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. , 1992, Science.

[2]  D. Selkoe,et al.  Amyloid β-peptide is produced by cultured cells during normal metabolism , 1992, Nature.

[3]  H. Y. Chen,et al.  Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. , 1992, The New England journal of medicine.

[4]  Thomas Wisniewski,et al.  Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid , 1992, Neuroscience Letters.

[5]  I. Drury,et al.  Allele‐specific sequencing confirms novel prion gene polymorphism in Creutzfeldt‐Jakob disease , 1991, Neurology.

[6]  A. Haase,et al.  Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes , 1991, Journal of virology.

[7]  C. Masters,et al.  Amyloid Precursor Protein (APP) and ΒZA4 Amyloid in the Etiology of Alzheimer's Disease: Precursor‐Product Relationships in the Derangement of Neuronal Function , 1991, Brain pathology.

[8]  M. Pericak-Vance,et al.  Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. , 1991, American journal of human genetics.

[9]  PhilipR. Wenham,et al.  Apolipoprotein E genotyping by one-stage PCR , 1991, The Lancet.

[10]  D. Selkoe.  The molecular pathology of Alzheimer's disease , 1991, Neuron.

[11]  E. Otomo,et al.  Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease , 1991, Brain Research.

[12]  D. T. Vernier,et al.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. , 1990, Journal of lipid research.

[13]  H. Cann,et al.  Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. , 1990, Genomics.

[14]  E. Shooter,et al.  A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. , 1989, The Journal of clinical investigation.

[15]  R. Mahley,et al.  Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. , 1988, Science.

[16]  R. E. Pitas,et al.  Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. , 1987, The Journal of biological chemistry.

[17]  R. Mahley,et al.  Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. , 1987, Biochimica et biophysica acta.

[18]  G. Schellenberg,et al.  Association of an apolipoprotein CII allele with familial dementia of the Alzheimer type. , 1987, Journal of neurogenetics.

[19]  J. Freeman,et al.  Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. Shooter,et al.  Expression of apolipoprotein E during nerve degeneration and regeneration. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Taylor,et al.  Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. , 1985, The Journal of clinical investigation.

[22]  J. Taylor,et al.  Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[23]  G. Assmann,et al.  Apolipoprotein E Polymorphism and Coronary Artery Disease , 1983, Arteriosclerosis.