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Article type: Research Article
Authors: Nyborg, Andrew C.a; * | Moll, Jonathan R.a | Wegrzyn, Renee D.a | Havas, Danielb | Hutter-Paier, Birgitb | Feuerstein, Giora G.Z.a | Rudolph, Alan S.a
Affiliations: [a] Adlyfe Inc., Rockville, MD, USA | [b] JSW Life Sciences GmbH, Grambach, Austria
Correspondence: [*] Correspondence to: Andrew C. Nyborg, Adlyfe Inc., 9430 Key West Avenue, Rockville, MD 20850, USA. Tel.: +1 301 424 8344; Fax: +1 301 424 8386; E-mail: andrewnyborg@gmail.com.
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.
Keywords: Alzheimer's disease, amyloid-β peptide, amyloid-β protein, imaging, oligomer, plaques, senile plaques
DOI: 10.3233/JAD-122107
Journal: Journal of Alzheimer's Disease, vol. 34, no. 4, pp. 957-967, 2013
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