Plasma amyloid β protein is elevated in late-onset Alzheimer disease families
- 19 February 2008
- journal article
- Published by Wolters Kluwer Health in Neurology
- Vol. 70 (8) , 596-606
- https://doi.org/10.1212/01.wnl.0000278386.00035.21
Abstract
Objective: Plasma Aβ levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD). Methods: We measured plasma Aβ in first-degree relatives of patients with LOAD in a cross-sectional series and in extended LOAD families. We screened these subjects for pathogenic mutations in early-onset AD genes and determined their ApoE genotypes. Results: Plasma Aβ is significantly elevated in the LOAD first-degree relatives in comparison to unrelated controls and married-in spouses. These elevations are not due to ApoE ε4 or pathogenic coding mutations in the known early-onset AD genes. Conclusions: The findings provide strong evidence for the existence of novel, as yet unknown genetic factors that affect late-onset Alzheimer disease by increasing Aβ.Keywords
This publication has 44 references indexed in Scilit:
- Elevated amyloid β protein (Aβ42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator geneHuman Molecular Genetics, 2004
- Genetic variants in a haplotype block spanningIDE are significantly associated with plasma A?42 levels and risk for Alzheimer diseaseHuman Mutation, 2004
- Biochemical detection of Aβ isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer’s diseaseBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2000
- Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In VivoNeuron, 1996
- Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer's diseaseThe Lancet, 1996
- Monte Carlo tests for associations between disease and alleles at highly polymorphic lociAnnals of Human Genetics, 1995
- Alzheimer's β‐amyloid peptide specifically interacts with and is degraded by insulin degrading enzymeFEBS Letters, 1994
- Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.Proceedings of the National Academy of Sciences, 1993
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993
- Clinical diagnosis of Alzheimer's diseaseNeurology, 1984