International Alzheimer's Disease Research Portfolio (IADRP) aims to capture global Alzheimer's disease research funding.

Alzheimer's disease (AD) is a recognized international public health crisis. There is an urgent need for public and private funding agencies around the world to coordinate funding strategies and leverage existing resources to enhance and expand support of AD research. To capture and compare their existing investments in AD research and research-related resources, major funding organizations are starting to utilize the Common Alzheimer's Disease Research Ontology (CADRO) to categorize their funding information.

Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project.

Alzheimer's disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer's disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer's disease research in the United States and internationally.

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies.

Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies.

Amyloid precursor protein compartmentalization restricts beta-amyloid production: therapeutic targets based on BACE compartmentalization.

Alzheimer's disease (AD) is defined by deposits of the 42-residue amyloid-beta peptide (Abeta42) in the brain. Abeta42 is a minor metabolite of the amyloid precursor protein (APP), but its relative levels are increased by mutations on APP and presenilins 1 and 2 linked to familial AD. beta-secretase (BACE-1), an aspartyl protease, cleaves approx 10% of the APP in neuronal cells on the N-terminal side of Abeta to produce the C-terminal fragment (CTFbeta), which is cleaved by gamma-secretase to produce mostly Abeta of 40 residues (90%) and approx10% Abeta42.

Apolipoprotein E4 as a target for developing new therapeutics for Alzheimer's disease.

The identification of factors that influence the onset or progression of the sporadic form of Alzheimer's disease (AD) is a key step toward understanding its mechanism(s) and developing successful rational therapies. The apoE genotype has been identified as a powerful risk factor for AD that may account for as much as 50% of the sporadic form of the disease. As the major risk factor for late-onset AD, apolipoprotein E4 (apoE4) should be considered a good target for AD drug discovery.

Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol.

Apolipoprotein E (ApoE) influences the risk of late onset Alzheimer's disease (AD) in an isoform-dependent manner, such that the presence of the apoE epsilon4 allele increases the risk of AD while the presence of the apoE epsilon2 allele appears to be protective. Although a number of ApoE functions are isoform dependent and may underlie the "risk factor" activity of AD, its ability to bind amyloid beta peptides and influence their clearance and/or deposition has gained strong experimental support. Evidence suggests that in addition to genotype, increased ApoE transcription can contribute to AD risk.

Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease.

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro.

Statin therapy for Alzheimer's disease: will it work?

Disease-modifying therapies are being developed for Alzheimer's disease (AD). These are expected to slow the clinical progression of the disease or delay its onset. Cerebral accumulation of amyloid beta (A beta) peptides is an early and perhaps necessary event for establishing AD pathology.

Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis.

Recent epidemiological, clinical, and experimental data suggest that cholesterol may play a role in Alzheimer's disease (AD). We have recently shown that cholesterolemia has a profound effect in the development and modulation of amyloid pathology in a transgenic model of AD. This review summarizes recent advancements in our understanding of the potential role of cholesterol and the amyloid beta protein in initiating the generation of free radicals and points out their role in a chain of events that causes damage of essential macromolecules in the central nervous system and culminates in neuronal dysfunction and loss.