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Absence of effect of chronic nicotine administration on amyloid beta peptide levels in transgenic mice overexpressing mutated human APP (Sw, Ind)

Bibliographic

Year of Publication:
2008
Contact PI Name:
Marwan N. Sabbagh
Contact PI Affiliation:
Cleo Roberts Center for Clinical Research, Sun Health Research Institute, Sun City, Arizona, USA
Co-Authors:
Douglas G.Walker, Richard T. Reid, Tiffany Stadnick, Keshav Anand, Lih-Fen Lue
Primary Reference (PubMED ID):
Funding Source:
Arizona Alzheimer’s Consortium
Sun Health Research Institute
Study Goal and Principal Findings:

Studies have indicated that nicotine has disease-modifying and cognitive-enhancing properties in Alzheimer's disease (AD). Nicotine has been proposed to be neuroprotective through anti-amyloid beta (Abeta) effects, anti-excitotoxic effects, and anti-free radical effects. Previously, conflicting data from Abeta plaque developing transgenic mice have shown significant Abeta-lowering effects, or alternatively no effects, of nicotine administration. In this study, dosing of transgenic mice (J20 strain) with mutated human APP (Swedish mutations: K670N and M671L and Indiana mutation: V717F) transgene, with nicotine in drinking water for 20 weeks did not have a significant effect on total levels of Abeta 40 or 42 in hippocampus or cortex. This treatment strategy resulted in increased levels of nicotinic acetylcholine receptor activity, and reduced levels of cortical glial fibrillary acidic protein, but had no effect on cortical synaptophysin protein levels. The J20 mouse strain produces higher levels of Abeta 42, the more pathogenic form of Abeta, than Abeta 40 compared to other Abeta plaque developing mouse strains; this could account for differences in effectiveness of nicotine in transgenic mice models of AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Nicotine
Therapeutic Target:
Nicotinic Cholinergic Receptor

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Biochemical
Nicotinic Cholinergic Receptor alpha 4/beta 2
Synaptophysin
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-Buffer Soluble beta Amyloid Peptide 40
Binding Affinity Measurements
Brain-Guanidine Soluble beta Amyloid Peptide 40
Brain-Guanidine Soluble beta Amyloid Peptide 42
Glial Fibrillary Acidic Protein (GFAP)
Nicotinic Cholinergic Receptor alpha 7 Subunit
Pharmacology
Binding Affinity