Albumin gene encoding free fatty acid and β‐amyloid transporter is genetically associated with Alzheimer disease

Abstract  Alzheimer disease (AD), the major cause of dementia in the elderly, is characterized by β‐amyloid deposition in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Since albumin, binding and transporting free fatty acids is also the major transporter of β‐amyloid, we examined the association between the albumin (ALB) gene and the occurrence of late‐onset AD (LOAD). We found that the allele distribution of the intron 4 microsatellite of the ALB gene showed a significant difference (P < 0.05) between LOAD (n = 285) and control group (n = 656). An allele with 11 CA repeat, termed (CA)11 allele, was significantly predominant in the control group (P < 0.005), and the odds ratio carrying the (CA)11 allele was 0.43 (P < 0.01, 95% CI = 0.24–0.79). Logistic regression indicated that this effect was independent of age and the ɛ4 dose of the apolipoprotein E gene (P < 0.01), while the ALB gene was supposed to be related to aging. Our results indicate that the ALB gene is genetically related with the occurrence of LOAD, supporting the link between fatty acid and β‐amyloid transport in the development of LOAD.

[1]  Y. Ishibashi,et al.  Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats , 2002, Journal of neurochemistry.

[2]  A A Spector,et al.  Fatty acid binding to plasma albumin. , 1975, Journal of lipid research.

[3]  L. Thal,et al.  late-onset Alzheimer’s disease , 2007 .

[4]  J. Haines,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. , 1997, JAMA.

[5]  M. Pericak-Vance,et al.  Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  T. Peters.  Serum albumin: recent progress in the understanding of its structure and biosynthesis. , 1977, Clinical chemistry.

[7]  Y. Ebihara,et al.  [The changes in physico-chemical parameters obtained from apparently healthy aged people followed over ten years]. , 1993, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics.

[8]  D. Lütjohann,et al.  Importance of a Novel Oxidative Mechanism for Elimination of Brain Cholesterol , 1997, The Journal of Biological Chemistry.

[9]  H. Braak,et al.  Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism. , 2003, Archives of neurology.

[10]  J. Dietschy,et al.  Cholesterol metabolism in the brain , 2001, Current opinion in lipidology.

[11]  J. Edmond.  Essential polyunsaturated fatty acids and the barrier to the brain , 2001, Journal of Molecular Neuroscience.

[12]  C. Schweiger.  [Statins and the risk of dementia]. , 2001, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[13]  K. Huse,et al.  Genetic and functional characteristics of the human in vivo LRP1/A2MR receptor suggested as a risk marker for Alzheimer’s disease and other complex (degenerative) diseases , 2004, Neuroscience Research.

[14]  K. Kamino,et al.  Gene dose effect of the APOE-ϵ4 allele on plasma HDL cholesterol level in patients with Alzheimer’s disease , 2002, Neurobiology of Aging.

[15]  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.

[16]  S. Arlt,et al.  Amyloid-β is an antioxidant for lipoproteins in cerebrospinal fluid and plasma , 2001 .

[17]  J. Haines,et al.  Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis , 1997 .

[18]  M. Tarnawski,et al.  A quantitative immunocytochemical study of blood-brain barrier to endogenous albumin in cerebral cortex and hippocampus of senescence-accelerated mice (SAM). , 1995, Folia histochemica et cytobiologica.

[19]  J. Poirier,et al.  The polymorphism in exon 3 of the low density lipoprotein receptor-related protein gene is weakly associated with Alzheimer's disease , 1999, Neuroscience Letters.

[20]  R. Katzman.,et al.  Modulation of amyloid beta-protein clearance and Alzheimer's disease susceptibility by the LDL receptor-related protein pathway. , 2000, The Journal of clinical investigation.

[21]  F. Jessen,et al.  Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease , 2002, Molecular Psychiatry.

[22]  D. Mengin-Lecreulx,et al.  Characterization of the Essential Gene glmM Encoding Phosphoglucosamine Mutase in Escherichia coli(*) , 1996, The Journal of Biological Chemistry.

[23]  F. Field,et al.  Effect of dietary n-3 fatty acids on HMG-CoA reductase and ACAT activities in liver and intestine of the rabbit. , 1987, Journal of lipid research.

[24]  D. Peterson,et al.  Amyloid beta peptide alters intracellular vesicle trafficking and cholesterol homeostasis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P. Elias,et al.  Epidermal HMG CoA reductase activity in essential fatty acid deficiency: barrier requirements rather than eicosanoid generation regulate cholesterol synthesis. , 1992, The Journal of investigative dermatology.

[26]  J. Kuret,et al.  Oxidative regulation of fatty acid-induced tau polymerization. , 2000, Biochemistry.

[27]  B. Hyman,et al.  Amyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma* , 1996, The Journal of Biological Chemistry.

[28]  D. Wilson,et al.  Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer's disease. , 1997, The American journal of pathology.