P1‐272: Intranasal administration of pronucleon peptides for in vivo imaging of beta‐amyloid in Alzheimer's disease
Year: 2008
Type: article
Abstract: One of the pathological features of Alzheimer's disease (AD) is the conversion of a normal soluble protein into insoluble beta amyloid aggregates. Aggregation and deposition of amyloid beta in vivo may precede clinical symptoms by many years. In vivo imaging of amyloid plaques would be beneficial for the following reasons: 1) A potential preclinical diagnostic of AD, 2) Determining the efficacy of anti-amyloid therapies, 3) Monitoring effects of AD therapeutics in clinical trials. We previously reported a novel Pronucleon peptide technology that specifically measures beta amyloid. The Pronucleon peptide undergoes a sequence-specific conformational change in the presence of the amyloid beta aggregates which can be used to measure beta amyloid in CSF and blood. The primary objective is to develop an easily administered imaging agent that will provide an early measure of plaque or amyloid aggregate burden associated with AD. The Pronucleon peptide was first examined as an ex vivo stain for amyloid plaques. We have since administered (intranasally) Pronucleon peptides in hAPP transgenic mice that develop extensive plaque pathology. Sections from these mice were subjected to ex vivo analyses including fluorescence, Thioflavin S staining, anti-amyloid staining and anti-GFAP staining. The Pronucleon peptides contain fluorescent tags that are sensitive to beta amyloid conformational states and results in the ability to image beta amyloid aggregates with a fluorescent microscope. Ex vivo administration of the Pronucleon peptide to tissue section from transgenic mice demonstrates that the peptide labels plaque like material. These, ex vivo, plaque-like images co merge with Thioflavin S staining. Intransal, in vivo, administration of the fluorescent Pronucleon peptide labels plaques in the hippocampus and cortex of transgenic mice. Fluorescent structures had plaque like morphology and co merged with anti-amyloid antibody or Thioflavin S staining. A significant positive correlation was observed between Pronucleon peptide staining and Thioflavin S staining. These data suggest that the Pronucleon peptide can efficiently cross the blood brain barrier, label plaques, and may be an effective tool for in vivo imaging.
Source: Alzheimer s & Dementia
Institution: Adlyfe (United States)
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2055730197