Genetic association of α2-macroglobulin with Alzheimer's disease in a Finnish elderly population

• Published in: Annals of neurology 1999-09, Vol.46 (3), p.382-390
• Main Authors: Myllykangas, Liisa, Polvikoski, Tuomo, Sulkava, Raimo, Verkkoniemi, Auli, Crook, Richard, Tienari, Pentti J., Pusa, Anna-Kaisa, Niinistö, Leena, O'Brien, Peter, Kontula, Kimmo, Hardy, John, Haltia, Matti, Pérez-Tur, Jordi
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Medical sciences; Neurology
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/1531-8249(199909)46:3<382::AID-ANA14>3.0.CO;2-5

Recently, two studies have reported an association between the α2‐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 α2‐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 α2‐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.