ArticleJournal of Alzheimer's disease : JAD2017
Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage.
Article in Journal of Alzheimer's disease : JAD, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.EMBO molecular medicine · 2018Trial
- Anti-pyroglutamate-3 Aβ immunotherapy engages microglia and inhibits amyloid accumulation in transgenic mouse models of Aβ amyloidosis.Acta neuropathologica · 2025Article
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Combination of Epigallocatechin-3-Gallate and Tramiprosate Prevent Accumulation of Intracellular Aβ and Dysfunctional Autophagy-Lysosomal Pathway at Earliest Stage of Transdifferentiation of Mesenchymal Stromal Cells into PSEN1 E280A Cholinergic-like Neurons.International journal of molecular sciences · 2025Article
- A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transgenic amyloid precursor protein mouse models of amyloidosis. Incomplete models for Alzheimer's disease but effective predictors of anti-amyloid therapies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging.Frontiers in aging neuroscience · 2021Article
- Article
- Clinical Trials in Alzheimer's Disease: A Hurdle in the Path of Remedy.International journal of Alzheimer's disease · 2020Review
- The β-secretase (BACE) inhibitor NB-360 in preclinical models: From amyloid-β reduction to downstream disease-relevant effects.British journal of pharmacology · 2019Review
- Production of seedable Amyloid-β peptides in model of prion diseases upon PrPNature communications · 2019Article
- A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease.Nature reviews. Neurology · 2019Review
- Canine Cognitive Dysfunction and Alzheimer's Disease - Two Facets of the Same Disease?Frontiers in neuroscience · 2019Review
- Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association.Journal of pathology informatics · 2019Review
- BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines.Frontiers in aging neuroscience · 2018Article
- Computer-Aided Multi-Target Management of Emergent Alzheimer's Disease.Bioinformation · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal Alzheimer's disease. Multiple anti-amyloid immunotherapies have been dose-limited by adverse amyloid related imaging abnormalities such as vasogenic edema (ARIA-E) and microhemorrhage (ARIA-H) observed in human trials and mice. Verubecestat was tested in a 12-week nonclinical study for the potential to exacerbate microhemorrhage (ARIA-H) profiles in 18-22-month-old post-plaque Tg2576-AβPPswe mice. Animals were treated with verubecestat or controls including the anti-Aβ antibody analog of bapineuzumab (3D6) as a positive control for ARIA induction. ARIA-H was measured using in-life longitudinal T2*-MRI and Prussian blue histochemistry at study end. Verubecestat reduced plasma and cerebrospinal fluid Aβ40 and Aβ42 by >90% and 62% to 68%, respectively. The ARIA-H profile of verubecestat-treated mice was not significantly different than controls. Anti-Aβ treatment significantly increased ARIA-H detected by Prussian blue staining; however, anti-Aβ antibody treatment did not impact plaque status. Verubecestat treatment significantly suppressed the accumulation of total levels of brain Aβ40 and Aβ42 and Thioflavin S positive plaque load. Stereological analysis of cortex and hippocampus plaque load similarly revealed significantly reduced area of Aβ immunoreactivity and reduced plaque number in verubecestat-treated animals compared to controls. The absence of elevated ARIA events in verubecestat-treated mice was associated with a significant reduction in the level of accumulated CNS amyloid pathology and brain Aβ peptides; effects consistent with the desired therapeutic mechanism of verubecestat in AD patients. These data will be compared with longitudinal MRI profiles from ongoing clinical trials.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.