There are nearly 50 million people with Alzheimer's disease (AD) worldwide and currently no disease modifying treatment is available. AD is characterized by deposits of Amyloid-β (Aβ), neurofibrillary tangles, and neuroinflammation, and several drug discovery programmes studies have focussed on Aβ as therapeutic target. Active immunization and passive immunization against Aβ leads to the clearance of deposits in humans and transgenic mice expressing human Aβ but have failed to improve memory loss. This review will discuss the possible explanations for the lack of efficacy of Aβ immunotherapy, including the role of a pro-inflammatory response and subsequent vascular side effects, the binding site of therapeutic antibodies and the timing of the treatment. We further discuss how antibodies can be engineered for improved efficacy.
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http://dx.doi.org/10.3389/fnins.2018.00254 | DOI Listing |
Alzheimers Res Ther
January 2025
UK Dementia Research Institute at Cardiff, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK.
Background: The success of selecting high risk or early-stage Alzheimer's disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer's disease (AD). Our study comprehensively examines AD PRS utility using various methods and models.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders", NeuroPresage Team, Institut Blood and Brain @ Caen-Normandie, GIP Cyceron, Bd Henri Becquerel, BP 5229, Caen, 14074, France.
Background: Subclinical depressive symptoms increase the risk of developing Alzheimer's disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brain regions involved in the stress response in older adults with or without subclinical depressive symptoms.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
MMDN, Univ Montpellier, EPHE, INSERM, Montpellier, France.
Background: Fluoroethylnormemantine (FENM), a new Memantine (MEM) derivative, prevented amyloid-β[25-35] peptide (Aβ)-induced neurotoxicity in mice, a pharmacological model of Alzheimer's disease (AD) with high predictive value for drug discovery. Here, as drug infusion is likely to better reflect drug bioavailability due to the interspecies pharmacokinetics variation, we analyzed the efficacy of FENM after chronic subcutaneous (SC) infusion, in comparison with IP injections in two AD mouse models, Aβ-injected mice and the transgenic APP/PSEN1 (APP/PS1) line.
Methods: In Aβ-treated mice, FENM was infused at 0.
Alzheimers Res Ther
January 2025
Center for Cognitive and Computational Neuroscience, Complutense University of Madrid, Pozuelo de Alarcón, 28223, Spain.
Background: Changes in amyloid beta (Aβ) and phosphorylated tau brain levels are known to affect brain network organization but very little is known about how plasma markers can relate to these measures. We aimed to address the relationship between centrality network changes and two plasma pathology markers: phosphorylated tau at threonine 231 (p-tau231), a proxy for early Aβ change, and neurofilament light chain (Nfl), a marker of axonal degeneration.
Methods: One hundred and four cognitively unimpaired individuals were divided into a high pathology load (33 individuals; HP) group and a low pathology (71 individuals; LP) one.
J Gen Intern Med
January 2025
Center for Health System Sciences, Atrium Health, Charlotte, NC, USA.
Background: Hypertension management is a national priority. However, hypertension control rates are suboptimal and vary across clinics, even among those in the same health system and geographic region.
Objective: To identify organizational barriers and facilitators that impact hypertension management at the provider, clinic, and health system level.
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