The Howard Hughes Medical Institute (HHMI), one of the most important private philanthropic organizations funding basic biomedical research in the USA, also supports the work of 90 International Scholars from ten countries in central and eastern Europe and the former Soviet Union. The grants awarded are quite small, but sufficient to allow them to continue internationally competitive research without joining the international `brain drain'; as Purnell Choppin, the president of HHMI, says: `It is very important for these countries to retain their scientists so they can create a good climate for science.' Delegates at a meeting of international scholars held in Budapest in June heard important work on Alzheimer's disease (AD) presented by two of these scholars: Professor Evgeny Rogaev (Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, Russia) and Professor Michal Novak (Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia).Professor Novak described AD as `a quiet epidemic of a greying mankind.' Certainly, this neurodegenerative disorder is a leading cause of morbidity and mortality throughout the developed world, and is estimated to cost US $80 billion yearly in the USA alone. Although statistical analysis is difficult where firm diagnosis is only possible post-mortem, some experts predict that there will be well over 30 million cases worldwide—with most in developing countries—by 2025.Neurofibrillary tangles are a classic pathological feature of AD. They consist of aggregates of paired helical filaments (PHFs) that are largely made up of a protein known as tau. Normal tau binds reversibly to, and stabilizes, microtubules, and is rapidly broken down by proteases. Tau found in PHFs is insoluble, protease resistant and abnormally phosphorylated. Professor Novak and his co-workers have established that this abnormal tau is truncated by about 20 residues at the C-terminus. In his talk in Budapest, he described a monoclonal antibody, MN423, that binds to truncated, but not normal, tau. Using this antibody, he has shown that up to 60% of neurons in the brains of AD patients that contained truncated tau also showed DNA fragmentation, which is an early sign of apoptosis (programmed cell death). This is a clear indication that tau truncation precedes DNA fragmentation and can induce apoptosis in neurons.Professor Rogaev played a leading part in the international consortium that discovered two genes with mutations associated with familial AD. The protein products of these genes—the presenilins—might play a role in the metabolism of the amyloid precursor protein and in apoptosis. Mutations in presenilin 1 are associated with the early-onset AD3 subtype of the disease. A correlation between the presence of the ϵ4 allele of the apolipoprotein E gene (APOE4) with susceptibility to late-onset AD is well known in Western European and white US populations, but is not found in other groups, such as African Americans. Rogaev presented an evaluation of the prevalence of this allele in association with early-onset and late-onset forms of AD, and other dementias, in a relatively small number of ethnic Russian dementia cases and age-matched controls. He found a strong correlation, similar to that in other Caucasians, between ϵ4 and AD; 12 AD cases and no controls were homozygous for this allele. However, over half of all cases of AD are not associated with a known mutation and, as Rogaev says, `There are probably a few genes with variations that might be associated with or protective from AD that are still unknown.'It is no exaggeration to say that this work might not have been possible without the financial support of HHMI. After the Velvet Revolution and the breakup of Czechoslovakia, the Slovak science budget was severely cut. In 1994, 50% of the scientists employed by the Slovak Academy of Sciences had to leave. The award of an HHMI grant is also an important sign of recognition by the international scientific community. Novak says: `In 1996, [partly due to] the international recognition represented by this HHMI grant, the Presidency of the Slovak Academy finally approved the setting up of our new Institute of Neuroimmunology'.After meeting at the first conference of international scholars in Prague in 1996, Professors Rogaev and Novak have established a productive collaboration. Their application to the European Union's INCO-COPERNICUS programme was one of only five projects graded as excellent. This grant, held in collaboration with researchers in Italy and Germany, will fund the APOE genotyping of larger Russian and eastern European populations, and studies of other Alzheimer's-related genes in these populations. They will also investigate interactions between mutant presenilins and tau metabolism that could lead to an acceleration of the molecular processes leading to neuronal cell death and thence to memory loss.