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Preferential deposition of amyloid beta protein (Abeta) in the form Abeta40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele.
Neurosci Lett 1997; 221(2-3):81-4NL

Abstract

The effect of apolipoprotein E (ApoE) genotype on the deposition of amyloid beta protein (Abeta) was examined in 54 patients with Alzheimer's disease. No difference in the amount of Abeta deposited as Abeta42(43) was seen between genotype groups with no, one or two E4 alleles. However, the amount of Abeta40 deposited increased according to the copy number of E4 alleles with patients possessing one E4 allele containing more than twice, and those with two E4 alleles, four times, the amount of Abeta40 in their brains compared to patients without an E4 allele. The increase in total Abeta deposited within the tissue (i.e. Abeta40 plus Abeta42(43) loads) in the presence of an E4 allele is therefore due entirely to an enhanced deposition of Abeta40. These data are consistent with the suggestion that the presence of E4 within pre-existing Abeta42(43) containing plaques may lower the threshold to fibrilization of Abeta40 thereby promoting its subsequent deposition. Thus, although the total amount of Abeta initially deposited in the brain as Abeta42(43) is not affected by the binding of any one particular ApoE isoform this does influence the subsequent maturation of plaques with a greater proportion transforming into Abeta40 containing cored plaques when the E4 isoform is present.

Authors+Show Affiliations

Department of Pathological Sciences, Division of Molecular Pathology, University of Manchester, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9121705

Citation

Mann, D M., et al. "Preferential Deposition of Amyloid Beta Protein (Abeta) in the Form Abeta40 in Alzheimer's Disease Is Associated With a Gene Dosage Effect of the Apolipoprotein E E4 Allele." Neuroscience Letters, vol. 221, no. 2-3, 1997, pp. 81-4.
Mann DM, Iwatsubo T, Pickering-Brown SM, et al. Preferential deposition of amyloid beta protein (Abeta) in the form Abeta40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele. Neurosci Lett. 1997;221(2-3):81-4.
Mann, D. M., Iwatsubo, T., Pickering-Brown, S. M., Owen, F., Saido, T. C., & Perry, R. H. (1997). Preferential deposition of amyloid beta protein (Abeta) in the form Abeta40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele. Neuroscience Letters, 221(2-3), pp. 81-4.
Mann DM, et al. Preferential Deposition of Amyloid Beta Protein (Abeta) in the Form Abeta40 in Alzheimer's Disease Is Associated With a Gene Dosage Effect of the Apolipoprotein E E4 Allele. Neurosci Lett. 1997 Jan 17;221(2-3):81-4. PubMed PMID: 9121705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preferential deposition of amyloid beta protein (Abeta) in the form Abeta40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele. AU - Mann,D M, AU - Iwatsubo,T, AU - Pickering-Brown,S M, AU - Owen,F, AU - Saido,T C, AU - Perry,R H, PY - 1997/1/17/pubmed PY - 1997/1/17/medline PY - 1997/1/17/entrez SP - 81 EP - 4 JF - Neuroscience letters JO - Neurosci. Lett. VL - 221 IS - 2-3 N2 - The effect of apolipoprotein E (ApoE) genotype on the deposition of amyloid beta protein (Abeta) was examined in 54 patients with Alzheimer's disease. No difference in the amount of Abeta deposited as Abeta42(43) was seen between genotype groups with no, one or two E4 alleles. However, the amount of Abeta40 deposited increased according to the copy number of E4 alleles with patients possessing one E4 allele containing more than twice, and those with two E4 alleles, four times, the amount of Abeta40 in their brains compared to patients without an E4 allele. The increase in total Abeta deposited within the tissue (i.e. Abeta40 plus Abeta42(43) loads) in the presence of an E4 allele is therefore due entirely to an enhanced deposition of Abeta40. These data are consistent with the suggestion that the presence of E4 within pre-existing Abeta42(43) containing plaques may lower the threshold to fibrilization of Abeta40 thereby promoting its subsequent deposition. Thus, although the total amount of Abeta initially deposited in the brain as Abeta42(43) is not affected by the binding of any one particular ApoE isoform this does influence the subsequent maturation of plaques with a greater proportion transforming into Abeta40 containing cored plaques when the E4 isoform is present. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/9121705/Preferential_deposition_of_amyloid_beta_protein__Abeta__in_the_form_Abeta40_in_Alzheimer's_disease_is_associated_with_a_gene_dosage_effect_of_the_apolipoprotein_E_E4_allele_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(96)13294-8 DB - PRIME DP - Unbound Medicine ER -