Deposition of extracellular Amyloid Beta (Aβ) and intracellular tau fibrils in post-mortem brains remains the only way to conclusively confirm cases of Alzheimer's Disease (AD). Substantial evidence, though, implicates small globular oligomers instead of fibrils as relevant biomarkers of, and critical contributors to, the clinical symptoms of AD. Efforts to verify and utilize amyloid oligomers as AD biomarkers in vivo have been limited by the near-exclusive dependence on conformation-selective antibodies for oligomer detection.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most prevalent cause of dementia and has become a health concern worldwide urging for an effective therapeutic. The amyloid hypothesis, currently the most pursued basis of AD drug discovery, points the cause of AD to abnormal production and ineffective removal of pathogenic aggregated amyloid-β (Aβ). AD therapeutic research has been focused on targeting different species of Aβ in the amyloidogenic process to control Aβ content and recover cognitive decline.
View Article and Find Full Text PDFAmyloid-β (Aβ) aggregated forms are highly associated with the onset of Alzheimer's disease (AD). Aβ abnormally accumulates in the brain and induces neuronal damages and symptoms of AD such as cognitive impairment and memory loss. Since an antibody drug, aducanumab, reduces Aβ aggregates and delays clinical decline, clearance of accumulated Aβ in the brain is accounted as a therapeutic approach to treat AD.
View Article and Find Full Text PDFAmyloid-β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aβ oligomers. Herein parallel and anti-parallel variants of Aβ(1-40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized.
View Article and Find Full Text PDFRecent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-β aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation.
View Article and Find Full Text PDFPurpose: Positron emission tomography/computer tomography (PET/CT) utilizing [(18)F]fluorodeoxyglucose ((18)F-FDG) has been recommended for the diagnosis, staging, therapy monitoring, prediction of prognosis, and detection of recurrence in endometrial cancer. We aimed to define the correlations of biological markers with (18)F-FDG uptake in endometrial cancer.
Methods: 29 patients (55 ± 8.