In the news

Hot on the heels of a paper suggesting that a common variant of the alph2-macroglobulin (A2M) gene on chromosome 12 is an important risk factor for late-onset Alzheimer's disease (see article in previous newsletter) come two new reports. One supports the suggestion of an Alzheimer's susceptiblity gene on chromosome 12 , but not in the region containing the A2M gene [Rogaeva, E. et al. (1998) JAMA 280, 614-618 (Summary)]. The other finds no evidence for a gene in this region, but a weak possibility of a gene in the A2M region, at least in those patients who do not carry an APOE4 allele [Wu, W.S. et al. (1998) JAMA 280, 619-622 (Summary)]. (See summary on Alzheimer's disease genetics for information on APOE gene variants and Alzheimer's risk).

Comment: Research on the genetics of Alzheimer's has progressed further than for any other psychiatric disease, but it is still bedevilled by many of the same problems discussed for schizophrenia genetics in the previous item. A lot hinges, too, on how the genetic studies are done: the two JAMA papers both used linkage analysis, whereas the A2M paper used an 'association' method with some similarity to the method that first picked up the APOE4 allele as an Alzheimer's risk factor (see summary on Alzheimer's disease for further details). Both methods have advantages and deficiencies; both can produce spurious results. Only further research can resolve the chromosome 12 question, but whatever the answer, the 'take-home message' is still the same: there is no justification for genetic testing for Alzheimer's disease susceptibility.