Genotyping and DNA banking
Since the discovery of the increased risk for Alzheimer’s disease that is attributable to the presence of the ε4 allele of the apolipoprotein E gene (apoE), numerous investigations have shown that some clinicopathologic characteristics of the disease are different in ε4 carriers vs non-carriers. Therefore it is important, when designing studies involving Alzheimer’s disease tissue, to analyze the data taking ε4 genotype into account. Since January 1999 it has been our objective to genotype every case coming to autopsy, with 730 cases done to date. The testing has been performed using a standard technique (Hixson and Vernier 1990), with DNA isolated from our lightly-fixed cerebellar samples as described previously (Beach et al. 2003). We have found this method more convenient than using fresh-frozen tissue although the method is unsuitable for brain tissue fixed in formalin for the standard interval of 10 days to 2 weeks; in these cases we use fresh-frozen cerebellum. We periodically perform quality control studies, having a series of our apoE-genotyped cases repeated by another laboratory. Isolated DNA remaining after apoE genotyping is stored for future studies. Screening for other mutations associated with neurodegenerative conditions (e.g. triplet repeat expansion diseases, spinocerebellar degenerations, progranulin mutations) is performed by outside collaborating laboratories when family history, clinical features and/or histopathology are suggestive of a particular condition.