Skip to main content
U.S. flag

An official website of the United States government

Aβ vaccination, but not nitro-nonsteroidal anti-inflammatory drug treatment, increases vascular amyloid and microhemorrhage while both reduce parenchymal amyloid


Year of Publication:
Contact PI Name:
Marcia N. Gordon
Contact PI Affiliation:
Alzheimer’s Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Science, College of Medicine, University of South Florida, Tampa, Florida, USA
D.M. Wilcock, P.T. Jantzen, Q. Li, D. Morgan
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Vaccination with Aβ1–42 and treatment with NCX-2216, a novel nitric oxide releasing flurbiprofen derivative, have each been shown separately to reduce amyloid deposition in transgenic mice and have been suggested as potential therapies for Alzheimer’s disease. This study treated doubly transgenic amyloid precursor protein and presenilin-1 (APP+PS1) mice with Aβ1–42 vaccination, NCX-2216 or both drugs simultaneously for 9 months. Results showed that all treatments reduced amyloid deposition, both compact and diffuse, to the same extent while only vaccinated animals, with or without non-steroidal anti-inflammatory drug (NSAID) treatment, showed increased microglial activation associated with the remaining amyloid deposits. Active Aβ vaccination resulted in significantly increased cerebral amyloid angiopathy and associated microhemorrhages, while NCX-2216 did not, in spite of similar reductions in parenchymal amyloid. Co-administration of NCX-2216 did not attenuate this effect of the vaccine. This is the first report showing that active immunization can result in increased vascular amyloid and microhemorrhage, as has been observed with passive immunization. Co-administration of an NSAID agent with Aβ vaccination does not substantially modify the effects of Aβ immunotherapy. The difference between these treatments with respect to vascular amyloid development may reflect the clearance-promoting actions of the vaccine as opposed to the production-modifying effects proposed for flurbiprofen.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 1-42
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Cyclooxygenase 1 (COX 1)

Animal Model

Model Information:
Model Type:
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
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


Outcome Measured
Outcome Parameters
Dense-core/Compact Plaques
beta Amyloid Load
Activated Microglia
Diffuse Plaques
Vascular beta Amyloid Deposits
Activated Microglia
Brain-beta Amyloid Deposits
Anti-beta Amyloid Antibody Titers
Target Engagement (Reduction beta Amyloid Peptide 40-Brain)
Target Engagement (Reduction beta Amyloid Peptide 42-Brain)
Body Weight