Modifying reaction time tasks parameters in the automated IntelliCage identifies heightened impulsivity and impaired attention in the 3xTg-AD model of Alzheimer's disease.

Background: The 3xTg-AD transgenic mouse model of Alzheimer's disease (AD) is an important tool to investigate the relationship between development of pathological amyloid-β (Aβ) and tau, neuroinflammation, and cognitive impairments. Traditional behavioral tasks assessing aspects of learning and memory, such as mazes requiring spatial navigation, unfortunately suffer from several shortcomings, including the stress of human handling and not probing species-typical behavior. The automated IntelliCage system was developed to circumvent such issues by testing mice in a social environment while measuring multiple aspects of cognition.

Assessing the Benefit of Dietary Choline Supplementation Throughout Adulthood in the Ts65Dn Mouse Model of Down Syndrome.

Background/objectives: Down syndrome (DS) is the most common cause of early-onset Alzheimer's disease (AD). Dietary choline has been proposed as a modifiable factor to improve the cognitive and pathological outcomes of AD and DS, especially as many do not reach adequate daily intake levels of choline. While lower circulating choline levels correlate with worse pathological measures in AD patients, choline status and intake in DS is widely understudied.

Inflammation and the pathological progression of Alzheimer's disease are associated with low circulating choline levels.

Deficiency of dietary choline, an essential nutrient, is observed worldwide, with ~ 90% of Americans being deficient. Previous work highlights a relationship between decreased choline intake and an increased risk for cognitive decline and Alzheimer's disease (AD). The associations between blood circulating choline and the pathological progression in both mild cognitive impairment (MCI) and AD remain unknown.

Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimer's disease.

Most Americans (∼90%) are deficient in dietary choline, an essential nutrient. Associations between circulating choline and pathological progression in Alzheimer's disease (AD) remain unknown. Here, we examined these associations and performed a metabolomic analysis in blood serum from severe AD, moderate AD, and healthy controls.

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer's disease hallmarks.

There is an urgent need to identify modifiable environmental risk factors that reduce the incidence of Alzheimer's disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase protein in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake.

Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders.

Background: Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders.

Temporal and brain region-specific elevations of soluble Amyloid-β in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.

Down syndrome (DS) is a leading cause of intellectual disability that also results in hallmark Alzheimer's disease (AD) pathologies such as amyloid beta (Aβ) plaques and hyperphosphorylated tau. The Ts65Dn mouse model is commonly used to study DS, as trisomic Ts65Dn mice carry 2/3 of the triplicated gene homologues as occur in human DS. The Ts65Dn strain also allows investigation of mechanisms common to DS and AD pathology, with many of these triplicated genes implicated in AD; for example, trisomic Ts65Dn mice overproduce amyloid precursor protein (APP), which is then processed into soluble Aβ fragments.

IntelliCage Automated Behavioral Phenotyping Reveals Behavior Deficits in the 3xTg-AD Mouse Model of Alzheimer's Disease Associated With Brain Weight.

Transgenic rodent models of Alzheimer's disease (AD) were designed to study mechanisms of pathogenesis and connect these mechanisms with cognitive decline. Measurements of cognition in rodents can be confounded, however, by human handling and interaction; the IntelliCage was created to circumvent these issues while measuring various facets of cognition in a social environment with water consumption as the primary motivator for task completion. Here, for the first time, we examined the behavioral performance of 3xTg-AD mice in the IntelliCage.

Identification of retinoblastoma binding protein 7 (Rbbp7) as a mediator against tau acetylation and subsequent neuronal loss in Alzheimer's disease and related tauopathies.

Evidence indicates that tau hyper-phosphorylation and subsequent neurofibrillary tangle formation contribute to the extensive neuronal death in Alzheimer's disease (AD) and related tauopathies. Recent work has identified that increased tau acetylation can promote tau phosphorylation. Tau acetylation occurs at lysine 280 resulting from increased expression of the lysine acetyltransferase p300.

Sex differences in the IntelliCage and the Morris water maze in the APP/PS1 mouse model of amyloidosis.

Transgenic rodent models were created to decipher pathogenic mechanisms associated with Alzheimer's disease (AD), and behavioral apparatuses such as the Morris water maze (MWM) are used to assess cognition in mice. The IntelliCage was designed to circumvent issues of traditional behavioral tests, such as frequent human handling. The motivation to complete IntelliCage tasks is water consumption, which is less stressful than escaping from a pool in the MWM.

Lifelong choline supplementation ameliorates Alzheimer's disease pathology and associated cognitive deficits by attenuating microglia activation.

Currently, there are no effective therapies to ameliorate the pathological progression of Alzheimer's disease (AD). Evidence suggests that environmental factors may contribute to AD. Notably, dietary nutrients are suggested to play a key role in mediating mechanisms associated with brain function.

Maternal choline supplementation ameliorates Alzheimer's disease pathology by reducing brain homocysteine levels across multiple generations.

The lack of effective treatments for Alzheimer's disease (AD) is alarming, considering the number of people currently affected by this disorder and the projected increase over the next few decades. Elevated homocysteine (Hcy) levels double the risk of developing AD. Choline, a primary dietary source of methyl groups, converts Hcy to methionine and reduces age-dependent cognitive decline.

Necroptosis activation in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by severe neuronal loss; however, the mechanisms by which neurons die remain elusive. Necroptosis, a programmed form of necrosis, is executed by the mixed lineage kinase domain-like (MLKL) protein, which is triggered by receptor-interactive protein kinases (RIPK) 1 and 3. We found that necroptosis was activated in postmortem human AD brains, positively correlated with Braak stage, and inversely correlated with brain weight and cognitive scores.

Two independent alleles at 6q23 associated with risk of rheumatoid arthritis.

To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.

Bridges and barriers to health: her story - Emirati women's health needs.

Health care services in the United Arab Emirates have developed rapidly in the last 30 years fueled by oil revenues. These services have been planned and provided predominantly by non-nationals, with mixed success. The authors identify aspects of the health care system and the sociocultural environment that create both barriers and bridges to holistic health for Emirati women.