Anti-Amyloid Therapies for Alzheimer's Disease: An Alzheimer Europe Position Paper and Call to Action.

The growing prevalence and burden of Alzheimer's disease has catalysed huge investments in research on its causes, diagnosis, treatment and care. After many high-profile failures, recent clinical trials of anti-amyloid drugs have marked a turning point for the field, leading to the approval of the first disease-modifying therapies for Alzheimer's disease by the FDA. It is now up to European regulators to determine whether there is sufficient evidence to approve these drugs for patients with mild cognitive impairment or mild dementia due to Alzheimer's disease. Here, we outline Alzheimer Europe's position on anti-amyloid therapies for Alzheimer's disease, which was adopted by the Board of Alzheimer Europe following consultations with our member associations and with the European Working Group of People with Dementia. Beyond questions of drug efficacy, safety and cost, we highlight important issues that must be addressed by industry, regulators, payers, healthcare systems and governments, to ensure that patients have timely, appropriate and equitable access to innovative treatments, regardless of their socio-economic background, insurance status, or place of residence. We also call for continued investment in research on treatments that might benefit people with more advanced Alzheimer's disease - as well as support and care services that can help people live well with dementia at all stages of the disease.

LOW PREVALENCE OF HAEMOSPORIDIANS IN BLOOD AND TISSUE SAMPLES FROM HUMMINGBIRDS.

Hummingbirds are vital members of terrestrial ecosystems, and because of their high metabolic requirements, they serve as indicators of ecosystem health. Monitoring the parasitic infections of hummingbirds is thus especially important. Haemosporidians, a widespread group of avian blood parasites, are known to infect hummingbirds, but little is known about the prevalence and diversity of these parasites in hummingbirds. The prevalence of haemosporidians in several hummingbird species was examined and we compared 4 different tissue types in detecting parasites by polymerase chain reaction (PCR). Blood samples from 339 individuals of 3 different hummingbird species were tested, and 4 individuals were found positive for haemosporidian infection, a prevalence of 1.2%. Hummingbird carcasses (n = 70) from 5 different hummingbird species were also sampled to assess differences in detection success of haemosporidians in heart, kidney, liver, and pectoral muscle tissue samples. Detection success was similar among tissue types, with haemosporidian prevalence of 9.96% in heart tissue, 9.52% in kidney tissue, 10.76% in liver tissue, and 11.76% in pectoral muscle tissue. All tissue samples positive for haemosporidian infection were from the Black-chinned Hummingbird (Archilochus alexandri). Possible reasons for low prevalence of these blood parasites could include low susceptibility to insect vectors or parasite incompatibility in these hummingbirds.

Detection and prevalence of Haemoproteus archilochus (Haemosporida, Haemoproteidae) in two species of California hummingbirds.

Haemosporidian blood parasites are transmitted to a wide range of avian hosts via blood-sucking dipteran vectors. Microscopy has revealed an impressive diversity of avian haemosporidia with more than 250 species described. Moreover, PCR and subsequent sequence analyses have suggested a much greater diversity of haemosporidia than morphological analyses alone. Given the importance of these parasites, very few studies have focused on the charismatic hummingbirds. To date, three Haemoproteus species (Haemoproteus archilochus, Haemoproteus trochili, and Haemoproteus witti) and one Leucocytozoon species (Leucocytozoon quynzae) have been described in blood samples taken from hummingbirds (Trochilidae). Unconfirmed Plasmodium lineages have also been detected in hummingbirds. Here, we report the detection of H. archilochus in two hummingbird species (Calypte anna and Archilochus alexandri) sampled in Northern California and perform a phylogenetic analysis of mitochondrial cytochrome b (cyt b) gene lineages. A total of 261 hummingbirds (157 C. anna, 104 A. alexandri) were sampled and screened for blood parasites using PCR and microscopy techniques. Combining both methods, 4 (2.55%) haemosporidian infections were detected in C. anna and 18 (17.31%) haemosporidian infections were detected in A. alexandri. Molecular analyses revealed four distinct H. archilocus cyt b lineages, which clustered as a monophyletic clade. No species of Plasmodium or Leucocytozoon were detected in this study, raising the possibility of specific vector associations with hummingbirds. These results provide resources for future studies of haemosporidian prevalence, diversity, and pathogenicity in California hummingbird populations.

Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus).

Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and FX-binding-ablated Ad5 vectors in non-human primates. Ad5 vectors accumulated in and mediated gene transfer predominantly to the liver, whereas FX-binding-ablated vectors primarily targeted the spleen but showed negligible liver gene transfer. In addition, we show that Ad5 binding to hepatocytes may be due to the presence of heparan sulfate proteoglycans (HSPGs) on the cell membrane. Therefore, the Ad5-FX-HSPG pathway mediating liver gene transfer in rodents is also the mechanism underlying Ad5 hepatocyte transduction in Microcebus murinus.