No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
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.
Blennow
K
K
Department of Clinical Neuroscience, University of Göteborg, Sahlgren's University Hospital, Mölndal, Sweden. kaj.blennow@ms.se
Ricksten
A
A
Prince
J A
JA
Brookes
A J
AJ
Emahazion
T
T
Wasslavik
C
C
Bogdanovic
N
N
Andreasen
N
N
Båtsman
S
S
Marcusson
J
J
Nägga
K
K
Wallin
A
A
Regland
B
B
Olofsson
H
H
Hesse
C
C
Davidsson
P
P
Minthon
L
L
Jansson
A
A
Palmqvist
L
L
Rymo
L
L
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D058225:Plaque, Amyloid / Q000473:pathology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D000511:alpha-Macroglobulins / Q000032:analysis / Q000134:cerebrospinal fluid / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D012333:RNA, Messenger; D000511:alpha-Macroglobulins