No association between the α2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression

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%), 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.

Original article On the lack of a clear-cut association between alpha-2-macroglobulin deletion and the risk of Alzheimer disease in Poland

“…Sequencing of the RT-PCR products from the deletion and insertion homozygotes revealed no alteration in sequence from that expected, despite the loss of 5 bp adjacent to exon 18. These molecular findings suggest that A2M deletion might be nonfunctional [6].…”

“…However, there are also many studies with negative results, including in Poland [21], Hungary [10], Japan [9], China [20], USA [22], Italy [17], Germany [3], France [8] and Sweden [6].…”

Identification and Functional Analysis of Differentially Expressed Genes Related to Metastatic Osteosarcoma

“…In general, A2M is a high-molecular weight homotetrameric glycoprotein and functions as a physiological guardian (Rehman et al, 2013). Many researches focus on its function in the Alzheimer's disease and depression (Blennow et al, 2000;Fujita et al, 2003), and few are in cancer even OS. Consequently, in order to articulate the roles of A2M in metastatic OS, we performed PPI network and identified its interactive proteins, for instance, IL1B, LRP1 and PDGF.…”

The Gothenburg MCI study: Design and distribution of Alzheimer’s disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up

“…After the first visit, apolipoprotein E (APOE) genotype is performed by minisequencing as described previously in detail. 48 Biochemical methods. Core CSF biomarker analyses, total tau protein (T-tau), phosphorylated tau (Ptau181), and amyloid beta (A 1-42) are performed after the CSF samples have been frozen once at À20 C for a maximum of 1 week.…”