Increased plasma apolipoprotein E (apoE) levels in Alzheimer's disease

We measured the concentration of apolipoprotein E (apoE) in plasma from 184 non-fasted subjects in order to determine whether important variations might exist linking plasma apoE levels to clinical phenotypes among early and late onset sporadic Alzheimer's disease (AD) and Down's syndrome (DS). A significant increase in the level of plasma apoE was observed in non-fasted late-onset AD patients (with a mean level of 3.26 +/- 0.08 microgram apoE/mg total protein for n = 84 patients) when compared with the plasma apoE levels of control individuals (mean of 2.32 +/- 0.10 microgram apoE/mg total protein, n = 51 patients; P < 0.001). A similar increase was found for non-fasted early-onset AD patients (mean of 3.69 +/- 0.17 microgram apoE/mg total protein, n = 20) when compared with the plasma apoE levels of control individuals (P < 0.001). Plasma apoE levels for DS patients did not differ significantly from those of controls (P > 0.05). The association of elevated plasma apoE levels in AD may be relevant to clarifying the mechanism(s) whereby apoE isoforms specify differential risk for development of AD.

[1]  M. Kawakami,et al.  A high frequency of apolipoprotein E4 isoprotein in Japanese patients with late-onset nonfamilial Alzheimer's disease , 1993, Neuroscience Letters.

[2]  M. Pericak-Vance,et al.  Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Pollen,et al.  Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease , 1995, Nature.

[4]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[5]  E M Wijsman,et al.  Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease , 1995, Neurology.

[6]  H. Wiśniewski,et al.  Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome , 1985, Annals of neurology.

[7]  A. Hofman,et al.  Apolipoprotein E4 allele in a population–based study of early–onset Alzheimer's disease , 1994, Nature Genetics.

[8]  P. Greengard,et al.  Alzheimer Amyloid-β Peptide Forms Denaturant-Resistant Complex with Type ε3 but Not Type ε4 Isoform of Native Apolipoprotein E , 1996, Molecular medicine.

[9]  A D Roses,et al.  Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Martins,et al.  Characterization of the Binding of Amyloid‐β Peptide to Cell Culture‐Derived Native Apolipoprotein E2, E3, and E4 Isoforms and to Isoforms from Human Plasma , 1997, Journal of neurochemistry.

[11]  A. D. Roses,et al.  Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease , 2006 .

[12]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[13]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Tateishi,et al.  Apolipoprotein E mRNA in the brains of patients with Alzheimer's disease , 1995, Journal of the Neurological Sciences.

[15]  M. Pericak-Vance,et al.  Apolipoprotein E ∈4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases , 1993, The Lancet.

[16]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[17]  R. Martins,et al.  ApoE genotypes in Australia: roles in early and late onset Alzheimer's disease and Down's syndrome , 1995, Neuroreport.

[18]  G. Getz,et al.  Isoform-specific binding of apolipoprotein E to beta-amyloid. , 1994, The Journal of biological chemistry.

[19]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.