Genetic association of ?2-macroglobulin with Alzheimer's disease in a Finnish elderly population

Myllykangas, Liisa; Polvikoski, Tuomo; Sulkava, Raimo; Verkkoniemi, Auli; Crook, Richard; Tienari, Pentti J.; Pusa, Anna-Kaisa; Niinist�, Leena; O’Brien, Peter C.; Kontula, Kimmo; Hardy, John; Haltia, Matti; P�rez-Tur, Jordi

doi:10.1002/1531-8249(199909)46:3<382::aid-ana14>3.0.co;2-5

Cited by 72 publications

(34 citation statements)

References 35 publications

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“…The significance of neuropathological definition of both cases and controls is highlighted by our previous report showing that the odds ratio for AD of APOE q4 is 19.6 in the neuropathologically verified Vantaa-85+ subpopulation [13], which is among the strongest reported to date. The corresponding odds ratio is only 2.88, when the clinical diagnostic criteria are used to differentiate patients and controls [13]. Our previous report of an association of AD with alpha-2-macroglobulin was confined to the neuropathologically defined group of AD and controls, no associations were detected in the clinically defined cases and controls [13].…”

Section: Discussionsupporting

confidence: 89%

“…Therefore the AD cases and the controls can be considered as extremely discordant phenotypes drawn from the same unselected Vantaa-85+ population. The significance of neuropathological definition of both cases and controls is highlighted by our previous report showing that the odds ratio for AD of APOE q4 is 19.6 in the neuropathologically verified Vantaa-85+ subpopulation [13], which is among the strongest reported to date. The corresponding odds ratio is only 2.88, when the clinical diagnostic criteria are used to differentiate patients and controls [13].…”

Section: Discussionmentioning

confidence: 88%

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Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: A two-stage study

Myllykangas

Vrièze

Polvikoski

et al. 2005

Journal of the Neurological Sciences

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 88%

Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: A two-stage study

Myllykangas

Vrièze

Polvikoski

et al. 2005

Journal of the Neurological Sciences

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“…A recent metaanalysis concluded that "A2M is not genetically associated with LOAD in white patients or mixed populations as found in the United States" [34]. This conclusion stands in opposition to at least nine independent reports finding significant association between polymorphisms in A2M and AD across various ethnic groups, using both casecontrol and family-based designs [29,32,[35][36][37][38][39][40][41]. And although only time will tell whether or not variation in A2M is a major genetic risk factor for AD, the growing number of confirmatory reports, even amidst multiple refutations, make it unlikely that the initial findings are due to type I error alone.…”

Section: Chromosome 12mentioning

confidence: 99%

Of replications and refutations: The status of Alzheimer’s disease genetic research

Bertram

Tanzi

2001

Curr Neurol Neurosci Rep

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Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date, mutations in three genes (APP, PSEN1, PSEN2) have been described to cause familial early-onset AD. In addition, a common polymorphism in the gene encoding apolipoprotein E (APOE) has been associated with the more common late-onset form of the disease. However, many studies have shown that genetic factors other than APOE play an important role in late-onset AD. Along these lines, a recent report predicted the existence of at least four additional late-onset AD genes, one of which was estimated to have a much greater contribution to age of onset variation than the APOE epsilon 4-allele. However, most of the nearly three dozen loci that have been proposed as putative AD genes to date have been followed by both replications and refutations, making consensus impossible. In this overview, we discuss the current status of genetic research in AD, including a brief summary of applicable analytic tools, and a summary of recent findings suggesting the existence of novel AD genes on chromosomes 10, 11, and 12.

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“…Genetic association of A2M with AD was also noted in the Finnish elderly population [16]. Similar results were reported in the USA [5,7,13].…”

Section: Introductionmentioning

confidence: 99%

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

Michałowska-Wender

Wawrzynek²,

G³

et al. 2014

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A b s t r a c t Alzheimer disease (AD) is a complex, multi-factorial disease with the potential involvement of several genes. Alpha-2-macroglobulin (A2M) has been implicated in AD on the basis of its ability to mediate the clearance and degradation of β-amyloid peptide. Nevertheless, it is not clear whether there are racial differences in frequency of polymorphisms of A2M in AD. We examined a group of 50 unrelated patients from Poland (38 women and 12 men), who were diagnosed clinically as probably developing AD (according to the N1NCD3 -ADR PA criteria). The patients were examined by a neurologist and a psychologist and had a CT or MRI scan of the brain. Fifty individuals of matched age, withoutany signs of dementia, were studied as a control group. DNA was extracted by a routine method from a blood sample. Amplification and genotyping at A2M was performed as described by Blacker et al. (1997). The genotypic distribution in A2M exon 18 in patients with AD and genotype TT in A2M exon 24 was similar to that in the controls. Significant differences were noted only in early onset AD in males and for old onset disease in females. The deletions were found more frequently in AD; however, they were found in only a small proportion of studied patients. These findings indicate that A2M is not the only biological candidate gene for AD determination.

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Genetic association of ?2-macroglobulin with Alzheimer's disease in a Finnish elderly population

Cited by 72 publications

References 35 publications

Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: A two-stage study

Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: A two-stage study

Of replications and refutations: The status of Alzheimer’s disease genetic research

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

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