Skip to main content
U.S. flag

An official website of the United States government

Transcutaneous beta-amyloid immunization reduces cerebral beta-amyloid deposits without T cell infiltration and microhemorrhage


Year of Publication:
Contact PI Name:
Jun Tan
Contact PI Affiliation:
Department of Psychiatry and Behavioral Medicine, Center for Excellence in Aging and Brain Repair, University of South Florida, Tampa, Florida, USA
William V. Nikolic, Yun Bai, Demian Obregon, Huayan Hou, Takashi Mori, Jin Zeng, Jared Ehrhart, R. Douglas Shytle, Brian Giunta, Morgan, Terrence Town
Primary Reference (PubMED ID):
Funding Source:
Alzheimer's Association
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

In this study the authors hypothesize that targeting Abeta immunotherapy to skin tissue might provide an immunotherapeutic approach that is both efficacious and safe. To test this hypothesis the investigators developed a transcutaneous (t.c.) Abeta vaccination approach and evaluated its efficacy and monitored for deleterious side effects, including meningoencephalitis and microhemorrhage. The data demonstrate that t.c. immunization of wild type mice with aggregated Abeta 1–42 plus the adjuvant cholera toxin (CT) results in high-titer Abeta antibodies (mainly of the Ig G1 class) and Abeta1–42-specific splenocyte immune responses. To evaluate the efficacy of t.c. immunization in reducing cerebral amyloidosis, transgenic PSAPP (APPsw, PSEN1dE9) mice were immunized with aggregated Abeta 1–42 peptide plus CT. Immunization with Abeta1–42 plus CT resulted in significant decreases in cerebral Abeta 1–40 and 1-42 levels coincident with increased circulating levels of Abeta 1–40,1-42, suggesting brain-to-blood efflux of Abeta.Reduction in cerebral amyloidosis was not associated with deleterious side effects, including brain T cell infiltration or cerebral microhemorrhage. Together, these data suggest that t.c. immunization constitutes an effective and potentially safe treatment strategy for AD.

Therapeutic Agent

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

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:

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
beta Amyloid Load
Plasma-beta Amyloid Peptide 40
Plasma-beta Amyloid Peptide 42
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
T Cell Response
Anti-beta Amyloid Antibody Titers
Anti-beta Amyloid Antibody Isotypes
Plasma-beta Amyloid Peptide 40
Plasma-beta Amyloid Peptide 42