Beth Borowsky
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View article: Reversibility of cognitive worsening observed with BACE inhibitor umibecestat in the Alzheimer's Prevention Initiative (API) Generation Studies
Reversibility of cognitive worsening observed with BACE inhibitor umibecestat in the Alzheimer's Prevention Initiative (API) Generation Studies Open
INTRODUCTION The Alzheimer's Prevention Initiative (API) Generation Studies evaluated the BACE inhibitor umibecestat for Alzheimer's disease (AD) prevention. The studies were terminated early, and the reversibility of umibecestat's side ef…
View article: A PET-CT study on neuroinflammation in Huntington’s disease patients participating in a randomized trial with laquinimod
A PET-CT study on neuroinflammation in Huntington’s disease patients participating in a randomized trial with laquinimod Open
Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington’s disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 …
View article: Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington’s disease
Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington’s disease Open
An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they e…
View article: An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion
An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion Open
Huntington’s Disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the huntingtin ( HTT ) gene. The mutant HTT (mHTT) protein causes neuronal dysfunction, causing progressive mo…
View article: Huntington’s Disease Integrated Staging System (HD-ISS): A Novel Evidence-Based Classification System For Staging
Huntington’s Disease Integrated Staging System (HD-ISS): A Novel Evidence-Based Classification System For Staging Open
Background Despite the monogenic autosomal dominant nature of Huntington’s disease (HD), the current research paradigm is still based on overt clinical phenotypes and does not address disease pathobiology and biomarkers that are evident de…
View article: The API Generation program: Umibecestat treatment and discontinuation effects on hippocampal and whole brain volumes in the overall population and amyloid‐negative APOE4 homozygotes
The API Generation program: Umibecestat treatment and discontinuation effects on hippocampal and whole brain volumes in the overall population and amyloid‐negative APOE4 homozygotes Open
Background In addition to early mild non‐progressive cognitive worsening, BACE inhibitors have been associated with early non‐progressive reductions in hippocampal and whole brain volume in trial participants with elevated amyloid (A+, Ega…
View article: The Generation program: Baseline characteristics of cognitively unimpaired APOE4 carriers recruited for Generation study 1 and Generation study 2
The Generation program: Baseline characteristics of cognitively unimpaired APOE4 carriers recruited for Generation study 1 and Generation study 2 Open
Background The Alzheimer Prevention Initiative (API) Generation Program evaluated the effectiveness of the BACE1 inhibitor, umibecestat, and the active immunotherapy, CAD106, in delaying the onset of AD symptoms in APOE4 carriers. The Gene…
View article: Longitudinal expression changes are weak correlates of disease progression in Huntington’s disease
Longitudinal expression changes are weak correlates of disease progression in Huntington’s disease Open
Huntington’s disease is a severe but slowly progressive hereditary illness for which only symptomatic treatments are presently available. Clinical measures of disease progression are somewhat subjective and may require years to detect sign…
View article: Association of CAG Repeats With Long-term Progression in Huntington Disease
Association of CAG Repeats With Long-term Progression in Huntington Disease Open
Results of this study suggest that succinct summary measures of function and brain loss characterize HD progression across a wide disease span. CAG repeat length strongly predicts their decline rate. This work aids our understanding of the…
View article: MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1
MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1 Open
The mismatch repair gene MSH3 has been implicated as a genetic modifier of the CAG·CTG repeat expansion disorders Huntington’s disease and myotonic dystrophy type 1. A recent Huntington’s disease genome-wide association study found rs55787…
View article: Design optimization for clinical trials in early‐stage manifest Huntington's disease
Design optimization for clinical trials in early‐stage manifest Huntington's disease Open
Objectives The purpose of this study was to inform the design of randomized clinical trials in early‐stage manifest Huntington's disease through analysis of longitudinal data from TRACK‐Huntington's Disease (TRACK‐HD), a multicenter observ…
View article: Natural variation in sensory‐motor white matter organization influences manifestations of Huntington's disease
Natural variation in sensory‐motor white matter organization influences manifestations of Huntington's disease Open
While the HTT CAG‐repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age‐at‐onset remains unexplained. Therefore, other factors …
View article: Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington’s Disease
Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington’s Disease Open
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanife…
View article: A Computational Cognitive Biomarker for Early-Stage Huntington’s Disease
A Computational Cognitive Biomarker for Early-Stage Huntington’s Disease Open
Huntington's disease (HD) is genetically determined but with variability in symptom onset, leading to uncertainty as to when pharmacological intervention should be initiated. Here we take a computational approach based on neurocognitive ph…
View article: Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance
Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance Open
Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints …