We appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β-amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

Species co-occurrence is an important ecological research area. Mark-and-recapture studies of mammals allow identification of coexisting species, a necessary step in determining mechanisms enabling habitat sharing. Using data from five 1-ha grids in January 2004 in tropical dry deciduous forest of coastal Colima, Mexico, we detected significantly more interspecific overlap than expected between seven species pairs. Oryzomys couesi shared more stations than expected with Sigmodon mascotensis, Baiomys musculus and Peromyscus perfulvus. Baiomys musculus was associated positively with S. mascotensis and Reithrodontomys fulvescens. Heteromys pictus shared fewer stations than expected with O. couesi and S. mascotensis. For species collectively, there was non-random community structuring, with two grids displaying more species aggregation than expected. While two grids had non-random co-occurrence patterns, three grids did not differ from random, which differs from that reported for mammalian taxa on average. Other small-mammal studies have documented species segregation, while this study detected more positive than negative associations. Similarities in preference and habitat use (or diet) are likely explanations for interspecific overlap patterns at stations and co-occurrence patterns among grids. Simultaneously evaluating associations of species pairs and all species on a grid collectively is novel methodology as applied to mammals, adding to understanding of species co-occurrence.

Tardive dyskinesia (TD) is a side-effect of chronic antipsychotic medication. Abnormalities in dopaminergic activity in the nigrostriatal system have been most often suggested to be involved because the agents which cause TD share in common potent antagonism of dopamine D2 receptors (DRD2), that notably is not balanced by effects such as more potent serotonin (5-HT)2A antagonism. Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD. The most consistent findings have been found with the Ser9Gly polymorphism of the DRD3 gene. Although DRD2 has long been hypothesized to be the main target for antipsychotics, only a few polymorphisms in DRD2 have been investigated for their potential involvement in the aetiology of TD. In the present study, we investigated 12 polymorphisms spanning the DRD2 gene and their association with TD in our European Caucasian (n=202) and African–American (n=30) samples. Genotype frequencies for a functional polymorphism, C957T (Duan et al., 2003; Hirvonen et al., 2004), and the adjacent C939T polymorphism were found to be significantly associated with TD (p=0.013 and p=0.022 respectively). DRD2 genotypes were not significantly associated with TD severity as measured by AIMS (Abnormal Involuntary Movement Scale) with the exception of a trend for C939T (p=0.071). Both TD and total AIMS scores were found to be significantly associated with two-marker haplotypes containing C939T and C957T (p=0.021 and p=0.0087 respectively). Preliminary results indicated that C957T was also associated with TD in our African–American sample (p=0.047). Taken together, the present study suggests that DRD2 may be involved in TD in the Caucasian population, although further studies are warranted.