title: In vivo and ex vivo imaging of amyloid-β cascade aggregates with a Pronucleon™ peptide.
abstract: Accumulation of amyloid-β (Aβ) cascade aggregates is considered a hallmark of Alzheimer's disease (AD). Current dogma holds that the appearance of Aβ oligomers and larger aggregates occur many years prior to plaque formation associated with the advanced and irreparable neurocognitive decline characteristic of AD. This premise is the impetus to identify these Aβ precursor structures prior to advanced plaque development. The Pronucleon™ technology platform is comprised of a novel series of engineered peptides that provide a unique readout when associated with beta-rich fiber and oligomeric Aβ. This technology has been applied to Ex Vivo tissue sections and In Vivo mouse models of AD to determine the potential utility of these synthetic peptides as potential imaging agents. In Ex Vivo studies, the Pronucleon™ peptide binds plaque like structures in brain sections obtained from transgenic mice overexpressing hAPP with both the human Swedish and London Aβ mutations. In Vivo, Pronucleon™ peptide administered peripherally can localize to the brain and label plaques throughout the brain in transgenic mice. Taken together, the data suggest that Pronucleon™ could provide a new imaging tool for Aβ cascade elements that precede advanced plaque and fibril formation, thereby advancing early diagnosis and treatment opportunities.
authors: Adlyfe Inc., Rockville, MD 20850, USA. andrewnyborg@gmail.com
authors: Andrew C
authors: AC
authors: Nyborg
authors: Jonathan R
authors: JR
authors: Moll
authors: Renee D
authors: RD
authors: Wegrzyn
authors: Daniel
authors: D
authors: Havas
authors: Birgit
authors: B
authors: Hutter-Paier
authors: Giora G Z
authors: GG
authors: Feuerstein
authors: Alan S
authors: AS
authors: Rudolph
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism; D020539:Sequence Analysis, Protein
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D010455:Peptides; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)