Alzheimer Disease: Chase GA

Bassett SS, Havstad SL, Chase GA. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · Genet Test. · Pubmed #15345108 No free full text.

Abstract: A survey questionnaire regarding perceptions of risk and genetic susceptibility to Alzheimer's disease (AD) was completed by 518 offspring of AD cases from families with multiple affected, ascertained as part of a genetic linkage study of late onset AD. The questionnaire focused on respondents' perceptions of their own risk for AD as well as on the properties of real and hypothetical susceptibility tests, including error rates for false-positive and false-negative test results. Our findings showed that about 20% of the sample would refuse a susceptibility test with zero error rates, about 40% would accept tests with very high error rates in both directions, and the remainder would exercise some discrimination. Acceptance of high test error rates was significantly associated with male gender, low education, and high perceived lifetime risk of AD. In a previous paper related to this work, we showed that physicians caring for these families exercised much more discrimination in judging the acceptability of genetic tests they would offer to these same respondents. The findings show that there is a pressing need to educate the public, particularly those with relatives affected by a complex disease, to expect standards of accuracy for genetic tests comparable to those that prevail in other diagnostic and prognostic testing efforts in the broad field of clinical medicine.

Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, Mahoney A, Beaty T, Fallin MD, Avramopoulos D, Chase GA, Folstein MF, McInnis MG, Bassett SS, Doheny KJ, Pugh EW, Tanzi RE, Anonymous00039. · Massachusetts General Hospital, Charlestown, MA, USA. · Hum Mol Genet. · Pubmed #12490529 links to  free full text

Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.

Chase GA, Geller G, Havstad SL, Holtzman NA, Bassett SS. · Department of Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Johns Hopkins University School of Mediicne, Baltimore, MD, USA. · Genet Med. · Pubmed #12172396 No free full text.

Abstract: PURPOSE: Examine physician knowledge, preferences, and use of genetic tests for Alzheimer's disease (AD). METHODS: Survey of 426 community-based physicians treating AD patients. RESULTS: Majority gave inaccurate estimates of AD risk. Medical specialty predicted appropriate use of current tests. Recommending substances to prevent memory loss was related to acceptance of error-free tests. High patient loads and familiarity with genetic tests predicted lower tolerance for test error. CONCLUSION: Physicians do not endorse indiscriminate genetic susceptibility testing for AD. However, insufficient knowledge of disease risk, etiology, genetic susceptibility, and use of existing tests indicated a need for further physician education in this area.