Exploring the stigma experienced by people affected by Parkinson's disease: a systematic review.

Background: Stigma significantly impacts individuals with Parkinson's disease (PD) and their caregivers, exacerbating social isolation, psychological distress, and reducing quality of life (QoL). Although considerable research has been conducted on PD's clinical aspects, the social and emotional challenges, like stigma, remain underexplored. Addressing stigma is crucial for enhancing well-being, fostering inclusivity and improving access to care and support.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) identified the ATP binding cassette subfamily A member 7 (ABCA7) gene as increasing risk for Alzheimer's disease (AD). ABC proteins transport various molecules across extra and intra-cellular membranes. ABCA7 is part of the ABC1 subfamily and is expressed in brain cells including neurons, astrocytes, microglia, endothelial cells and pericytes.

Basic Science and Pathogenesis.

Background: Late-onset Alzheimer's disease (LOAD) is the leading cause of dementia and a major contributor to increased mortality. Recent human datasets have revealed many LOAD genetic risk factors that are correlated with the degree of AD burden. Further, the complexity and heterogeneity of LOAD appears to be promoted by interactions between genetics and environmental factors such as diet, sedentary behavior, and exposure to toxicants, like lead (Pb), cadmium (Cd), and arsenic (As).

Basic Science and Pathogenesis.

Background: Determining the precise genetic mechanisms that contribute to LOAD, both in coding and noncoding variants, will enable a deeper understanding of pathogenesis and advance preclinical models for the testing of targeted therapeutics.

Methods: We have introduced candidate genetic variants in the EPHA1, BIN1, CD2AP, SCIMP, KLOTHO, PTK2B, ADAMTS4, IL1RAP, IL34, and PTPRB loci into a sensitized mouse model already harboring humanized amyloid-beta, APOE4, and Trem2.R47H alleles knocked in to a C57BL/6J background.

Basic Science and Pathogenesis.

Background: Data from human and model organism studies suggest that genetic background influences susceptibility and resilience to Alzheimer's Disease (AD) neuropathology. We previously showed that, wild-derived PWK/PhJ (PWK) mice carrying the APP/PS1 transgene (PWK.APP/PS1) exhibit cognitive and synaptic resilience compared to traditionally-studied B6.

Basic Science and Pathogenesis.

Background: The infectious hypothesis of Alzheimer's disease (AD) suggests that microbes may play a role in pathogenesis by triggering the pathologic cascade or contributing to disease progression. Herpesviruses, such as Epstein-Barr virus (EBV), have been of high interest in AD and related neurodegenerative diseases, in part due to their ability to establish lifelong latent infection and potentially reactivate. However, further research is needed to fully understand the role of herpesviruses in these diseases.

Basic Science and Pathogenesis.

Background: The microtubule-associated Tau gene (MAPT) undergoes alternative splicing to produce isoforms with varying combinations of microtubule-binding region (MTBR) repeats (3R, 4R). The MTBR is the predominant region that forms paired helical filaments and neurofibrillary tangles fibrils in disease. Alzheimer's disease (AD) is a mixed Tauopathy containing both 3R and 4R isoforms.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a complex, multifactorial pathology with high heterogeneity in biological alterations. Our understanding of cellular and molecular mechanisms from disease risk variants to various phenotypes is still limited. Mouse models of AD serve as indispensable platforms for comprehensively characterizing AD pathology, disease progression, and biological mechanisms.

Basic Science and Pathogenesis.

Background: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically-engineered marmosets that carry knock-in (KI) point mutations in the presenilin-1 (PSEN1) gene that can be studied from birth throughout lifespan.

Method: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) therapeutics have largely been unsuccessful in alleviating disease burden in those afflicted by the disease. The TREAT-AD Consortium is an international group of academic researchers dedicated to identifying novel molecular targets for AD from underexplored areas of disease linked pathology.

Method: Utilizing a top-down expert curation approach of organizing Gene Ontology terms into endophenotypes of AD, we developed 19 biological domains.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common form of dementia, yet the effectiveness of disease-modifying interventions is inconclusive. Although exceptional progress in our understanding of AD neuropathology has been made via transgenic mouse models bearing familial mutations, they often fail to recapitulate the disease progression of late-onset AD (LOAD). To address this, MODEL-AD has developed LOAD1 and LOAD2 mouse models which carry the most common human-relevant risk factors for AD.

Basic Science and Pathogenesis.

Background: Altered lipid profiles and lipid processing genes are associated with Alzheimer's disease (AD). There is a reported genetic interaction between the AD risk gene APOE and cholesterol ester transfer protein (CETP). Mice lack functional CETP which is critical to the balance of circulating lipoproteins; this imparts cardioprotective effects and may make mice resistant to AD.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) and other neurodegenerative diseases are typified by a robust microglial-mediated immune response. Genetic studies have demonstrated that variants in microglial genes are linked to risk for AD. Genome-wide association studies (GWAS) originally identified Phospholipase C gamma 2 (PLCγ2) as a novel risk gene of Alzheimer's disease (AD).

Basic Science and Pathogenesis.

Background: The genetic etiology of late-onset Alzheimer's disease (LOAD) is complex, with over 75 identified loci contributing to disease risk. Recent efforts of the MODEL-AD consortia have yielded several dozen mouse strains harboring variation designed to model LOAD risk alleles. Given the complex genetic architecture of LOAD, developing animal models that combine multiple risk alleles is likely essential to improving the fidelity of these models to human disease.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common global cause of dementia, with no real cure available. Despite extensive genetic findings from large-scale genetic associations and similar studies, our understanding of AD is largely hindered by its long, asymptomatic progression with limited access to human brain tissue. Animal models like the marmoset allow for longitudinal analysis of disease by enabling the assaying of disease-specific phenotypes that mimic human pathophysiology.

Basic Science and Pathogenesis.

Background: Apolipoprotein E4 (APOE4), a common variant of APOE, is a major genetic risk factor for Alzheimer's disease (AD), but APOE4 carriers do not always develop AD. Several large-scale genetic studies have identified a common haplotype of the aging factor klotho that modify disease risk in APOE4 carriers. In humans, klothoharbors two common missense variants (rs9536314, p.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) research has been historically dominated with studies in mouse models expressing familial AD mutations; however, the majority of AD patients have the sporadic, late-onset form of AD (LOAD). To address this gap, the IU/JAX/PITT MODEL-AD Consortium has focused on development of mouse models that recapitulate LOAD by combining genetic risk variants with environmental risk factors and aging to enable more precise models to evaluate potential therapeutics. The present studies were undertaken to characterize cognitive and neurophysiological phenotypes in LOAD mice.

ALSUntangled #77: Psilocybin.

ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation.

Methadone clinic staff perceptions of trauma-informed and patient-centered care: the role of individual staff characteristics.

Background: U.S. policy intervention to increase methadone treatment accommodations during COVID did not result in national adoption of the new patient-centered treatment practices.

Nurse-Led Mobile Phone Intervention to Promote Self-Management in Type 2 Diabetes in Ghana: A Randomized Controlled Trial.

Purpose: The purpose of the study was to test the effectiveness of a nurse-led mobile phone intervention (NMPI) on glycemic variability and self-management among people living with type 2 diabetes (T2DM) in Ghana.

Methods: In this randomized controlled trial, the intervention group received a 3-month NMPI program plus standard care, and the control group received standard care alone in a tertiary health care setting. Ninety-eight participants (baseline A1C > 7%) were randomized 1:1 to either NMPI or standard care group.

Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool.

Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.

Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.

Design, Setting, And Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population.

Marmosets as model systems for the study of Alzheimer's disease and related dementias: Substantiation of physiological tau 3R and 4R isoform expression and phosphorylation.

Introduction: Marmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied.

Methods: Isoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining.

Bupropion Toxicity Causing Refractory Cardiogenic Shock Successfully Treated With Mechanical Circulatory Support: A Case Report.

Bupropion is a norepinephrine-dopamine reuptake inhibitor that is commonly used as an antidepressant and for smoking cessation. Bupropion overdose can lead to serious side effects which include seizures, status epilepticus, and fatal arrhythmias. Managing bupropion toxicity is challenging as there is no effective antidote and treatment is largely supportive.

Evaluating a Kid's Dementia Awareness Game with Pre-Licensure Children and Young People's Nursing (CYP) Students in Northern Ireland - A Pre/Posttest Study.

Dementia not only affects the person living with the condition but also their family and wider social circle. For that reason, it is important to educate family members, the wider public and health professionals. How a child and young people's (CYP) nurse supports and responds to a CYP whose family member has dementia or acts as a carer is of interest to pre-licensure (pre-registration) CYP nursing programs.