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Background: Availability of amyloid modifying therapies will dramatically increase the need for disclosure of Alzheimer's disease (AD) related genetic and/or biomarker test results. The 21st Century Cares Act requires the immediate return of most medical test results, including AD biomarkers. A shortage of genetic counselors and dementia specialists already exists, thus driving the need for scalable methods to responsibly communicate test results.
View Article and Find Full Text PDFBackground: Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils. In two clinical studies (phase 2, NCT01767311 and phase 3 ClarityAD, NCT03887455) in early Alzheimer's disease, lecanemab substantially reduced amyloid PET and significantly slowed clinical decline on multiple measures of cognition and function, including CDR-SB at 18 months. Models describing the change in amyloid PET and CDR-SB in response to lecanemab treatment were used to explore the impact of changing from the initial dosage regimen (10 mg/kg every 2 weeks [Q2W]) to a less intensive maintenance dosing regimen (10 mg/kg every 4 weeks [Q4W]) on clinical efficacy, and to explore the optimal duration of the initial dosing regimen.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.
Background: The vicious cycle between depression and dementia increases the risk of Alzheimer's Disease (AD) pathogenesis and pathology. This study investigates therapeutic effectiveness versus side effects and the underlying mechanisms of intranasal dantrolene nanoparticles (IDNs) to treat depression behavior and memory loss in 5XFAD mice.
Method: 5XFAD and wild-type B6SJLF1/J mice were treated with IDNs (IDN, 5 mg/kg) in Ryanodex formulation for a duration of 12 weeks.
Drug Development.
Alzheimers Dement
December 2024
School of Pharmacy, Chapman University, Irvine, CA, USA.
Background: Although novel treatments for Alzheimer's disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Centre for Addiction and Mental Health, Toronto, ON, Canada.
Background: Dysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5-containing GABAA receptors (α5-GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5-positive allosteric modulator (α5-PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice.
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