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Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., light-chain and(More)
Chronic neuroinflammation correlates with cognitive decline and brain atrophy in Alzheimer's disease (AD), and cytokines and chemokines mediate the inflammatory response. However, quantitation of cytokines and chemokines in AD brain tissue has only been carried out for a small number of mediators with variable results. We simultaneously quantified 17(More)
Presenilin-1 (PS-1) mutations can cause Pick's disease without evidence of Alzheimer's disease (AD). We describe a family with a PS-1 M146L mutation and both Pick bodies and AD. Sarkosyl-insoluble hyperphosphorylated tau showed three bands consistent with AD, although dephosphorylation showed primarily three-repeat isoforms. M146L mutant PS-1 may predispose(More)
The assembly of amyloidogenic proteins into toxic oligomers is a seminal event in the pathogenesis of protein misfolding diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, hereditary amyotrophic lateral sclerosis, and type 2 diabetes. Owing to the metastable nature of these protein assemblies, it is difficult to assess their oligomer(More)
abstract Abnormal protein folding and self-assembly causes over 30 cureless human diseases for which no disease-modifying therapies are available. The common side to all these diseases is formation of aberrant toxic protein oligomers and amyloid fibrils. Both types of assemblies are drug targets, yet each presents major challenges to drug design, discovery,(More)
Aptamers are useful molecular recognition tools in research, diagnostics, and therapy. Despite promising results in other fields, aptamer use has remained scarce in amyloid research, including Alzheimer's disease (AD). AD is a progressive neurodegenerative disease believed to be caused by neurotoxic amyloid beta-protein (Abeta) oligomers. Abeta oligomers(More)
Alzheimer's disease (AD) is a progressive, age-dependent, neurodegenerative disorder with an insidious course that renders its presymptomatic diagnosis difficult 1. Definite AD diagnosis is achieved only postmortem, thus establishing presymptomatic, early diagnosis of AD is crucial for developing and administering effective therapies 2,3. Amyloid β-protein(More)
  • Inna Solomonov, Eduard, Korkotian, Benjamin Born, Yishay Feldman, Arkady Bitler +4 others
  • 2012
Background: The mechanism by which interaction between A␤ and Zn 2ϩ induces A␤ aggregation and cell toxicity is elusive. Results: Zn 2ϩ and A␤40 form metastable neurotoxic oligomers. Conclusion: A␤40 binding to Zn 2ϩ leads to formation of small neurotoxic oligomers that become benign upon further self-assembly. Significance: We provide a structure-function(More)
Self-assembly of amyloid β-protein (Aβ) into neurotoxic oligomers and fibrillar aggregates is a key process thought to be the proximal event leading to development of Alzheimer's disease (AD). Therefore, numerous attempts have been made to develop reagents that disrupt this process and prevent the formation of the toxic oligomers and aggregates. An(More)