ApoE ϵ3‐haplotype modulates Alzheimer beta‐amyloid deposition in the brain |
| |
| Authors: | Liisa Myllykangas Tuomo Polvikoski Karoliina Reunanen Fabienne Wavrant‐De Vrieze Clare Ellis Dena Hernandez Raimo Sulkava Kimmo Kontula Auli Verkkoniemi Irma‐Leena Notkola John Hardy Jordi Perez‐Tur Matti J. Haltia Pentti J. Tienari |
| |
| Affiliation: | 1. Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;2. Department of Neurology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;3. Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida;4. Department of Public Health and General Practice and Medicine, University of Kuopio, Kuopio, Finland;5. Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;6. Population Research Unit, University of Helsinki, Helsinki, Finland;7. Unitat de Genètica Molecular, Institut de Biomedicina de València‐CSIC, Valencia, Spain |
| |
| Abstract: | ![]()
ApoE ?4 allele increases the risk of late‐onset Alzheimer disease (AD) as well as the amount of beta‐amyloid deposition in the brain. Because half of AD patients do not have ApoE ?4, it is important to search for other determinants of ApoE that modify AD risk. We tested whether the haplotype background of the most common ApoE allele, ?3, influences brain amyloid deposition or the risk of neuropathologically verified AD in a population‐based sample of elderly Finns. To exclude the effects of ApoE protein polymorphism we focused these analyses on subjects homozygous for ?3. Haplotypes were defined using polymorphisms at positions ? 491 and ? 219 of the ApoE promoter and at position +113 of intron‐1. We found that ?3‐haplotypes containing the promoter allele ? 219T were associated with reduced amyloid deposition and reduced risk of neuropathologically verified AD as compared to ?3‐haplotypes containing ? 219G. The functional polymorphism(s) responsible for the haplotypic difference remains to be identified. These results indicate that there is significant allelic variation in the ApoE gene region, which modulates brain amyloid deposition and AD risk, independent of the ApoE protein polymorphism. © 2002 Wiley‐Liss, Inc. |
| |
| Keywords: | neuropathology aging dementia genetics |
|
|
