Real-world Site Experiences With GeneMatch: The Role of a Recruitment-related Registry in the Context of Local Site Effort to Support Alzheimer Disease Prevention Research.

BACKGROUND: Registries have been proposed as a novel way to accelerate targeted recruitment for Alzheimer disease prevention clinical trials. However, there are limited data regarding registry effectiveness at accelerating recruitment and enrollment in research opportunities. This manuscript explores one site's experience with GeneMatch, a novel genetic registry for Alzheimer disease research. METHODS: Referrals from GeneMatch to the site were tracked to understand the demographics of those referred and ultimate research enrollment outcomes. Referrals were cross-referenced with the site's existing recruitment database, to better understand the role of GeneMatch in the context of existing recruitment efforts. RESULTS: GeneMatch referred 86 individuals to the site, resulting in 54 individuals coming into the site to pursue research involvement further. The majority of referrals (52/86, 60.47%) did not have prior contact with the site about research engagement, and having prior site contact did not significantly relate to engaging in on-site research. CONCLUSIONS: GeneMatch helped identify new individuals for participation in Alzheimer disease prevention studies. Results highlight the value of continuing local site-level efforts while also taking advantage of registries to enhance research recruitment. Ongoing efforts to further develop these and other novel strategies for outreach and engagement are much needed.

Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy.

Accumulation of hyperphosphorylated tau directly correlates with cognitive decline in Alzheimer's disease and other primary tauopathies. One therapeutic strategy may be to reduce total tau expression. We identified antisense oligonucleotides (ASOs) that selectively decreased human tau mRNA and protein in mice expressing mutant P301S human tau. After reduction of human tau in this mouse model of tauopathy, fewer tau inclusions developed, and preexisting phosphorylated tau and Thioflavin S pathology were reversed. The resolution of tau pathology was accompanied by the prevention of hippocampal volume loss, neuronal death, and nesting deficits. In addition, mouse survival was extended, and pathological tau seeding was reversed. In nonhuman primates, tau ASOs distributed throughout the brain and spinal cord and reduced tau mRNA and protein in the brain, spinal cord, and cerebrospinal fluid. These data support investigation of a tau-lowering therapy in human patients who have tau-positive inclusions even after pathological tau deposition has begun.

Show Me My Health Plans: a study protocol of a randomized trial testing a decision support tool for the federal health insurance marketplace in Missouri.

BACKGROUND: The implementation of the ACA has improved access to quality health insurance, a necessary first step to improving health outcomes. However, access must be supplemented by education to help individuals make informed choices for plans that meet their individual financial and health needs. METHODS/DESIGN: Drawing on a model of information processing and on prior research, we developed a health insurance decision support tool called Show Me My Health Plans. Developed with extensive stakeholder input, the current tool (1) simplifies information through plain language and graphics in an educational component; (2) assesses and reviews knowledge interactively to ensure comprehension of key material; (3) incorporates individual and/or family health status to personalize out-of-pocket cost estimates; (4) assesses preferences for plan features; and (5) helps individuals weigh information appropriate to their interests and needs through a summary page with "good fit" plans generated from a tailored algorithm. The current study will evaluate whether the online decision support tool improves health insurance decisions compared to a usual care condition (the healthcare.gov marketplace website). The trial will include 362 individuals (181 in each group) from rural, suburban, and urban settings within a 90 mile radius around St. Louis. Eligibility criteria includes English-speaking individuals 18-64 years old who are eligible for the ACA marketplace plans. They will be computer randomized to view the intervention or usual care condition. DISCUSSION: Presenting individuals with options that they can understand tailored to their needs and preferences could help improve decision quality. By helping individuals narrow down the complexity of health insurance plan options, decision support tools such as this one could prepare individuals to better navigate enrollment in a plan that meets their individual needs. The randomized trial was registered in clinicaltrials.gov (NCT02522624) on August 6, 2015.

Antisense reduction of tau in adult mice protects against seizures.

Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.