ArticleAlzheimer's & dementia (New York, N. Y.)2021
Lanabecestat: Neuroimaging results in early symptomatic Alzheimer's disease.
Article in Alzheimer's & dementia (New York, N. Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.The journal of prevention of Alzheimer's disease · 2021Trial
- Bridging the gaps in alzheimer's disease: a comprehensive review of current and emerging therapies.Inflammopharmacology · 2026Review
- Key Chemotypes for the Rational Design of Dual AChE/BACE-1 Inhibitors.Current medicinal chemistry · 2026Review
- Therapeutic Advances in Targeting the Amyloid-β Pathway for Alzheimer's Disease.Brain sciences · 2025Review
- Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment.Materials today. Bio · 2025Article
- Recent Advances in Therapeutics for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Review
- Review on anti-alzheimer drug development: approaches, challenges and perspectives.RSC advances · 2024Review
- A review of the flortaucipir literature for positron emission tomography imaging of tau neurofibrillary tangles.Brain communications · 2024Review
- Consistency between Treatment Effects on Clinical and Brain Atrophy Outcomes in Alzheimer's Disease Trials.The journal of prevention of Alzheimer's disease · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
- BACE1 Inhibitors for Alzheimer's Disease: The Past, Present and Any Future?Molecules (Basel, Switzerland) · 2022Review
- Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Lanabecestat: Neuroimaging results in early symptomatic Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionLanabecestat, a beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inhibitor, was investigated as a potential Alzheimer's disease (AD)-modifying treatment. As previously reported, amyloid beta (Aβ) neuritic plaque burden reduction did not result in clinical benefit. Lanabecestat's effects on neuroimaging biomarkers and correlations between neuroimaging biomarkers and efficacy measures are reported.
methodsAMARANTH and DAYBREAK-ALZ were 104- and 78-week, multicenter, randomized, double-blind, placebo-controlled studies of lanabecestat in early symptomatic AD (AMARANTH) and mild AD dementia (DAYBREAK-ALZ). Patients randomly (1:1:1) received placebo, lanabecestat 20 mg, or lanabecestat 50 mg daily (AMARANTH, n = 2218; DAYBREAK-ALZ, n = 1722). Florbetapir positron emission tomography (PET), fluorodeoxyglucose (FDG) PET, flortaucipir PET, and volumetric magnetic resonance imaging (MRI) were used to measure Aβ neuritic plaque burden, cerebral metabolism, aggregated tau neurofibrillary tangles, and brain volume, respectively. Additionally, florbetapir perfusion scans were performed in DAYBREAK-ALZ. Efficacy measures included 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, Clinical Dementia Rating-Sum of Boxes, Functional Activities Questionnaire, and Mini-Mental State Examination. These studies stopped early due to futility.
resultsDespite previously observed annualized reduction in Aβ neuritic plaque burden, there were no treatment differences in annualized change of aggregated tau neurofibrillary tangle burden (AMARANTH, n = 284; DAYBREAK-ALZ, n = 70), cerebral metabolism (AMARANTH, n = 260; DAYBREAK-ALZ, n = 38) and perfusion (DAYBREAK-ALZ, n = 213). Greater brain volume reduction (AMARANTH, n = 1697 [whole brain]; DAYBREAK-ALZ, n = 650 [whole brain]) occurred on lanabecestat compared to placebo. Higher baseline aggregated tau neurofibrillary tangle burden, lower cerebral metabolism, and lower brain volumes correlated with poorer baseline efficacy scores and greater clinical worsening. Lower baseline cerebral perfusion correlated with poorer baseline efficacy scores. Reduction in cerebral metabolism or whole brain volume correlated with clinical worsening, regardless of treatment assignment. DISCUSSION: Tau pathology and cerebral metabolism assessments showed no evidence of lanabecestat slowing pathophysiologic progression of AD. Lanabecestat exposure was associated with brain volume reductions. Correlations between imaging measures and cognitive assessments may aid future study design.
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