No association between the α2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression
| Autor: | N Andreasen, Lars Rymo, Katarina Nägga, Jan Marcusson, Björn Regland, Kaj Blennow, A Jansson, C Hesse, Lennart Minthon, Anders Wallin, Hasse Olofsson, Anthony J. Brookes, Anne Ricksten, Nenad Bogdanovic, Jonathan A. Prince, Stellan Båtsman, Pia Davidsson, Tesfai Emahazion, C Wasslavik, L Palmqvist |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Genotype Apolipoprotein E4 Blotting Western Molecular Sequence Data Gene Expression Plaque Amyloid Biology White People Exon Apolipoproteins E Gene Frequency Alzheimer Disease Internal medicine Gene expression medicine Humans Genetic Predisposition to Disease alpha-Macroglobulins RNA Messenger Allele Gene Allele frequency Biological Psychiatry Aged Genetics Polymorphism Genetic Base Sequence Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis DNA medicine.disease Psychiatry and Mental health Endocrinology Neurology Electrophoresis Polyacrylamide Gel Female Neurology (clinical) Alzheimer's disease Gene Deletion |
| Zdroj: | Journal of Neural Transmission. 107:1065-1079 |
| ISSN: | 1435-1463 0300-9564 |
| DOI: | 10.1007/s007020070052 |
| Popis: | A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink