Bibliographic
Year of Publication:
2012
Contact PI Name:
Ken-ichiro Fukuchi
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
National Eye Institute (NEI)
Study Goal and Principal Findings:
We evaluated the therapeutic efficacy of combined treatment of Aβ-immunization with simvastatin in an Alzheimer mouse model at age 22 months. DNA prime-adenovirus boost immunization induced modest anti-Aβ titers and simvastatin increased the seropositive rate. Aβ-KLH was additionally administered to boost the titers. Irrespective of simvastatin, the immunization did not decrease cerebral Aβ deposits but increased soluble Aβ and tended to exacerbate amyloid angiopathy in the hippocampus. The immunization increased cerebral invasion of leukocytes and simvastatin counteracted the increase. Thus, modest anti-Aβ titers can increase soluble Aβ and simvastatin may reduce inflammation associated with vaccination in aged Alzheimer mouse models.
Therapeutic Agent
Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Simvastatin
Therapeutic Target:
HMG-CoA Reductase
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
AdPEDI-(Abeta 1-6)11 (AAV Encoding 11 Tandem Repeats of Abeta1-6)
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
pCA-PEDI-(Aβ1–6)11
Therapeutic Target:
beta Amyloid Peptide
Therapeutic Notes:
AdPEDI-(Aβ1–6)11 and pCA-PEDI-(Aβ1–6)11 were prepared as previously described: Kim, H.D., Maxwell, J.A., Kong, F.K., Tang, D.C., Fukuchi, K., 2005. Induction of antiinflammatory immune response by an adenovirus vector encoding 11 tandem repeats of Abeta1–6: toward safer and effective vaccines against Alzheimer's disease. Biochem. Biophys. Res. Commun. 336, 84–92.
Animal Model
Model Information:
Species:
Mouse
Model Type:
APPxPS1
Model Name:
APPswe/PSEN1dE9 (line 85)
Strain/Genetic Background:
(C57BL/6 x C3H)F2
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
Histopathology
beta Amyloid Load
Cerebral Amyloid Angiopathy (CAA)
Activated Microglia
Activated Astrocytes
Microhemorrhages
Biochemical
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Plasma-Total Cholesterol
Cytokines
Chemokines
Immunology
Anti-beta Amyloid Antibody Titers
Anti-beta Amyloid Antibody Isotypes
Toxicology
Transaminases
Creatinine