Inhibition of cerebral amyloid beta-protein deposition seems to be an important target for Alzheimer's disease therapy. Amyloidogenesis could be inhibited by short synthetic peptides designed as beta-sheet breakers. Here we demonstrate a 5-residue peptide that inhibits amyloid beta-protein fibrillogenesis, disassembles preformed fibrils in vitro and prevents neuronal death induced by fibrils in cell culture. In addition, the beta-sheet breaker peptide significantly reduces amyloid beta-protein deposition in vivo and completely blocks the formation of amyloid fibrils in a rat brain model of amyloidosis. These findings may provide the basis for a new therapeutic approach to prevent amyloidosis in Alzheimer's disease.
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http://dx.doi.org/10.1038/nm0798-822 | DOI Listing |
Alzheimers Dement
January 2025
Department of Neuroscience, City University of Hong Kong, Hong Kong, Hong Kong.
Introduction: Antisense oligonucleotides (ASOs) have shown promise in reducing amyloid precursor protein (APP) levels in neurons, but their effects in astrocytes, key contributors to neurodegenerative diseases, remain unclear. This study evaluates the efficacy of APP ASOs in astrocytes derived from an individual with Down syndrome (DS), a population at high risk for Alzheimer's disease (AD).
Methods: Human induced pluripotent stem cells (hiPSCs) from a healthy individual and an individual with DS were differentiated into astrocytes.
Alzheimers Dement
January 2025
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Introduction: Plasma phosphorylated tau (p-tau) biomarkers have improved Alzheimer's disease (AD) diagnosis, but data from diverse Asian populations are limited. This study evaluated plasma p-tau217 and p-tau181 levels in Korean and Taiwanese populations.
Methods: All participants (n = 270) underwent amyloid positron emission tomography (PET) and blood tests.
Front Immunol
January 2025
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, accounting for approximately 70% of dementia cases worldwide. Patients gradually exhibit cognitive decline, such as memory loss, aphasia, and changes in personality and behavior. Research has shown that mitochondrial dysfunction plays a critical role in the onset and progression of AD.
View Article and Find Full Text PDFBackground: Although Amyloid-beta and Tau are the hallmarks of Alzheimer's Disease (AD), other protein pathways such as endothelial dysfunction may be involved and may precede cognitive symptoms. Our objective was to characterize the cerebrospinal fluid (CSF) proteomic profiles focusing on cardiometabolic-related protein pathways in individuals on the AD spectrum.
Methods: We performed CSF and plasma-targeted proteomics (276 proteins) from 354 participants of the Brain Stress Hypertension and Aging Program (BSHARP), of which 8% had preclinical AD, and 24% had MCI due to AD.
PNAS Nexus
January 2025
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, 1-1-1 Daigaku-dori, Sanyo Onoda City, Yamaguchi 756-0884, Japan.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory impairment. The pathophysiology of AD may involve aggregated amyloid β (Aβ) accumulation, which may underlie the disease mechanism. Patients with diabetes exhibit an elevated risk of developing AD, indicating potential therapeutic implications upon elucidating the underlying mechanisms.
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