Aug 28, 2019

Active Amyloid-β Vaccination Results in Epigenetic Changes in the Hippocampus of an Alzheimer's Disease-Like Mouse Model

Current Alzheimer Research
Roy LardenoijeCynthia A Lemere

Abstract

While evidence accumulates for a role of epigenetic modifications in the pathophysiological cascade of Alzheimer's disease (AD), amyloid-β (Aβ)-targeted active immunotherapy approaches are under investigation to prevent or slow the progression of AD. The impact of Aβ active vaccines on epigenetic markers has not been studied thus far. The current study aims to establish the relationship between active immunotherapy with a MER5101-based vaccine (consisting of Aβ1-15 copies conjugated with a 7 aa spacer to the diphtheria toxoid carrier protein, formulated in a Th2-biased adjuvant) and epigenetic DNA modifications in the hippocampus of APPswe/PS1dE9 mice. As we previously reported, immunotherapy started when the mice were 10 months of age and behavioral testing occurred at 14 months of age, after which the mice were sacrificed for further analysis of their brains. In this add-on study, global levels of DNA methylation and hydroxymethylation, and DNA methyltransferase 3A (DNMT3A) were determined using quantitative immunohistochemistry, and compared to our previously analyzed immunization-induced changes in AD-related neuropathology and cognition. Active immunization did not affect global DNA methylation levels but instead, resulted...Continue Reading

  • References35
  • Citations1

Mentioned in this Paper

Biological Markers
Study
Immunohistochemistry
Genome
Immunologic Adjuvants
Vaccines
Brain
DNA Methylation
Alzheimer's Disease
Evaluation

Related Feeds

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Alzheimer's Disease: Genetics

Alzheimer's disease is a chronic neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations here.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques. Here is the latest research.

Alzheimer's Disease: Neuroimaging

Alzheimer's disease (AD) is a chronic neurodegenerative disease. Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.