. In vivo preclinical administration of a novel peptide based imaging agent for Alzheimer's disease. Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;

Abstract:

One of the pathological features of Alzheimer's disease (AD) is the conversion of a normal soluble protein, amyloid beta (Ab) into aggregates of its monomeric form. Contemporary science holds that Ab oligomers and larger aggregates, believed to contribute to neurocognitive deficits, may precede AD plaque burden by many years providing a window in which to diagnose AD earlier and monitor progression prior to advanced and irreparable neurocognitive decline. This premise is dependent on means to identify Ab cascade elements earlier than advanced plaques, such as Ab oligomers/aggregates. Adlyfe has been developing unique peptides, Pronucleon., that preferentially recognize Ab oligomers and aggregates by specifically binding to epitopes unique to misfolded, beta-sheet docking sites. The Pronucleon. peptide undergoes a sequence-specific conformational change in the presence of the amyloid beta aggregates which results in intense fluorescence as a result of the association of N-and C-terminal pyrene additives. Using Pronucleon. peptides, we have demonstrated ex vivo plaque specific staining of brain sections obtained from hAPP over-expressing mice bearing the Swedish/London genetic mutations (APPSL) that cause excessive plaque formation in the brain along with neurological deficits commensurate with human AD. These, ex vivo, fluorescent bodies are plaque like in morphology and correlate well with ThioflavinS staining (positive control). In addition, Pronucleon. peptides were administered in vivo via peripheral administration to APPSL mice that develop extensive plaque pathology and quantitatively visualized. The Pronucleon. peptide labeled plaques in the hippocampus and cortex of these transgenic mice. Furthermore, ex vivo labeling of post mortem human AD brain tissue sections demonstrated that Ab amyloid structures were labeled and co-stained with either Thioflavin S or anti-Ab 6E10. Taken together, Adlyfe Pronucleon. technology holds the promise of providing a new imaging tool for Ab cascade elements that precede advanced plaque and fibril formation thereby providing early diagnosis and treatment opportunities.

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