Alzheimer disease (AD), the most common cause of dementia in the elderly, exists in both familial and sporadic forms. Genetic studies have led to the identification of 3 genes, beta-amyloid precursor protein (APP), presenilin-1 (PS1), and presenilin-2 (PS2), which, when mutated, can cause familial forms of AD. Mutations in each of these genes result in elevated levels of A beta42/43, a proteolytic processing fragment of APP that is deposited in brains of AD patients. Transgenic mice carrying AD-causing mutations in APP develop spontaneous age-related beta-amyloid (A beta) deposition and memory impairment. Genetic linkage and association studies have also shown that the epsilon4 allele of the apolipoprotein E (APOE) gene increases risk for AD in a dose-dependent manner in both familial and sporadic forms of AD and may account for as much as 50% of the attributable risk. APOE genotyping may be useful both as an adjunct to diagnosis and in identifying patient groups for therapeutic intervention. While the biological basis for the association of APOE epsilon4 with AD is not known, age of onset and A beta deposition are positively correlated with epsilon4 allele dosage in some cases, suggesting that this risk may also be mediated directly or indirectly through A beta. Because 50% of AD cases have no APOE epsilon4 alleles and families showing mendelian inheritance of AD exist in whom there are no mutations in any of the APP, PS1, or PS2 genes, it is likely that there are additional AD risk factors, both genetic and environmental, still to be identified.

The genes which encode glycosomal glyceraldehyde‐phosphate dehydrogenase (gGAPDH) of Trypanosoma cruzi are arranged as a tandemly repeated pair on a single chromosome and are identical at the level of nucleotide sequence. They are separated by an intergenic region which contains a 317 base pair sequence with the properties of a retroposon. The genes express a 1.5 kb mRNA and a 38 kd protein. The amino acid sequence contains features characteristic of glycosomal enzymes such as peptide insertions and a C‐terminal extension. However, T. cruzi gGAPDH lacks one of the positively charged ‘hotspot’ motifs which have been proposed as topogenic signals for import into the glycosome, a unique microbody‐like organelle. Molecular modelling of the T. cruzi and T. brucei enzymes suggests that neither structure would fulfil the requirements of the ‘hotspot’ glycosomal import model.

Enhancement of trypanosomatid metacyclogenesis by insect urine components led us to test the effect of human urine as a culture additive. The addition of 1-5% urine to Schneider's Drosophila medium containing 10% foetal calf serum enhanced the growth of 11 Leishmania strains representing 8 different taxonomic groups. Cell division was stimulated in cultures with non-dividing organisms. Peak cell density was increased, as was the efficiency with which L. donovani could be isolated from infected hamsters. Preliminary work suggested that the modified medium would be useful for field isolation of L. donovani and L. braziliensis. The active nutrients or growth factors are not known.

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