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Genetic association of α 2 ‐macroglobulin with Alzheimer's disease in a Finnish elderly population
Author(s) -
Myllykangas Liisa,
Polvikoski Tuomo,
Sulkava Raimo,
Verkkoniemi Auli,
Crook Richard,
Tienari Pentti J.,
Pusa AnnaKaisa,
Niinistö Leena,
O'Brien Peter,
Kontula Kimmo,
Hardy John,
Haltia Matti,
PérezTur Jordi
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199909)46:3<382::aid-ana14>3.0.co;2-5
Subject(s) - apolipoprotein e , senile plaques , alzheimer's disease , degenerative disease , population , pathology , macroglobulin , disease , genetic association , genotype , medicine , biology , genetics , gene , single nucleotide polymorphism , environmental health
Recently, two studies have reported an association between the α 2 ‐macroglobulin gene on chromosome 12 and late‐onset Alzheimer's disease, whereas others have not been able to replicate these findings. By using a prospective population‐based study, we have investigated the relation between two polymorphisms in this gene with the presence of the disease and also with the extent of pathological changes in the cerebral cortex. The Vantaa 85+ Study includes all 601 persons, at least 85 years of age, who were living in Vantaa, Finland, on April 1, 1991. The neocortical β‐amyloid protein load and the number of neurofibrillary tangles were determined on tissue sections by using methenamine silver staining and a modified Bielschowsky staining, respectively. The A/A genotype in exon 24 of the α 2 ‐macroglobulin gene was associated with neuropathologically defined diagnosis of Alzheimer's disease according to the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria and with an increase in the neocortical β‐amyloid protein load. The effect of this association was stronger in the apolipoprotein E ε4–negative group. Therefore, genetic variability in the α 2 ‐macroglobulin gene is a risk factor associated with neuropathologically defined Alzheimer's disease in our population, as well as with the extent of neocortical β‐amyloid protein deposition.