Mean age of onset in familial Alzheimer's disease is determined by amyloid beta 42
- 11 November 2004
- journal article
- research article
- Published by Elsevier BV in Neurobiology of Aging
- Vol. 26 (6), 785-788
- https://doi.org/10.1016/j.neurobiolaging.2004.08.002
Abstract
More than 130 known mutations in the presenilin-1 (PS1) gene result in familial Alzheimer's disease (FAD) with a mutation specific age of disease onset. These mutations increase amyloid beta 42 (Aβ42) levels, and this increase has been validated in recent years as one pathogenic factor in FAD. However, further malfunctions of mutant presenilin-1 are discussed as well. In order to assess the weight of Aβ42 regarding the pathogenesis of FAD, we expressed mutant forms of PS1 (30–65 years onset age) in COS-7 cells and analyzed amyloid beta levels by a novel ELISA. We found a strong correlation (r = 0.98; p < 0.001) between the Aβ40/42-ratio and mean age of disease onset indicating a substantial extent of Aβ42 contribution to FAD pathology. Our data strongly suggest that Aβ42 is the decisive factor for age of onset in FAD.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- European Commission (QLK 2002-00172)
This publication has 19 references indexed in Scilit:
- Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretaseHuman Molecular Genetics, 2003
- The over-expression of the wild type or mutant forms of the presenilin-1 protein alters glycoprotein processing in a human neuroblastoma cell lineNeuroscience Letters, 2003
- γ-Secretase Cleavage Site Specificity Differs for Intracellular and Secretory Amyloid βJournal of Biological Chemistry, 2003
- Capacitive Calcium Entry Is Directly Attenuated by Mutant Presenilin-1, Independent of the Expression of the Amyloid Precursor ProteinPublished by Elsevier BV ,2003
- Mortality with Dementia: Results from a French Prospective Community-based CohortAmerican Journal of Epidemiology, 2001
- Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in miceNature Medicine, 1999
- Accelerated Amyloid Deposition in the Brains of Transgenic Mice Coexpressing Mutant Presenilin 1 and Amyloid Precursor ProteinsNeuron, 1997
- Alzheimerʼs PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptideNeuroReport, 1996
- Analysis of Heterogeneous βA4 Peptides in Human Cerebrospinal Fluid and Blood by a Newly Developed Sensitive Western Blot AssayPublished by Elsevier BV ,1996
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993