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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression

Blennow, K; Ricksten, A; Prince, J A; Brookes, A J; Emahazion, T; Wasslavik, C; Bogdanovic, N; Andreasen, N; Batsman, S and Marcusson, J, et al. (2000) In Journal of Neural Transmission 107(8-9). p.1065-1079
Abstract
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%),... (More)
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. (Less)
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Journal of Neural Transmission
volume
107
issue
8-9
pages
1065 - 1079
publisher
Springer
external identifiers
  • wos:000088951700016
  • scopus:0033626319
ISSN
0300-9564
DOI
10.1007/s007020070052
language
English
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yes
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53a16022-b2d8-4525-98ff-66e6a921df12 (old id 1297001)
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2009-07-15 13:27:05
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2017-08-13 04:19:47
@article{53a16022-b2d8-4525-98ff-66e6a921df12,
  abstract     = {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 &lt; 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.},
  author       = {Blennow, K and Ricksten, A and Prince, J A and Brookes, A J and Emahazion, T and Wasslavik, C and Bogdanovic, N and Andreasen, N and Batsman, S and Marcusson, J and Nägga, Katarina and Wallin, A and Regland, B and Olofsson, H and Hesse, C and Davidsson, P and Minthon, Lennart and Jansson, A and Palmqvist, L and Rymo, L},
  issn         = {0300-9564},
  language     = {eng},
  number       = {8-9},
  pages        = {1065--1079},
  publisher    = {Springer},
  series       = {Journal of Neural Transmission},
  title        = {No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression},
  url          = {http://dx.doi.org/10.1007/s007020070052},
  volume       = {107},
  year         = {2000},
}