An editorial in the BMJ urges caution about the much-vaunted announcement that a common mutation in the alpha2-microglobulin (A2M) gene may be a risk factor for late-onset Alzheimer's disease (see recent Newsletter item) [Edwardson, J. and Morrison, C. (1998) BMJ 317, 361-362 (link to full text, from this Web site only, by permission of the BMJ)]. Writing after the 6th International Conference on Alzheimer's Disease and Related Disorders, held recently in Amsterdam, the authors point out that several groups at the conference said they had not been able to confirm the association, which was uncovered by an approach called 'family-based association', in which the genotype of individuals with Alzheimer's disease was compared with the genotype of their unaffected siblings. Population-based studies are needed before the A2M mutation can be confirmed as an Alzheimer's risk factor.
Comment: A salutary reminder that no genetic association or linkage can be considered firm - especially in the field of psychiatric and behavioural genetics - until it is independently confirmed. But the public health conclusions remain the same: whether the A2M association is confirmed or not, there is at present no justification for presymptomatic testing for genetic risk factors for late-onset Alzheimer's disease.