Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Cholesterol and Abeta aggregation.

K Yanagisawa1

  • 1Department of Dementia Research, National Institute for Longevity Sciences, Morioka, Obu, Japan. katuhiko@nils.go.jp

Pharmacopsychiatry
|October 24, 2003
PubMed
Summary

Alzheimer's disease (AD) research reveals cholesterol accelerates amyloid beta-protein (Abeta) binding to GM1 ganglioside (GM1), forming seeds. ApoE4 mice show higher membrane cholesterol, suggesting a link to AD risk.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

TTF-1/NKX2-1 binds to DDB1 and confers replication stress resistance to lung adenocarcinomas.

Oncogene·2017
Same author

Expressive visual text-to-speech as an assistive technology for individuals with autism spectrum conditions.

Computer vision and image understanding : CVIU·2016
Same author

Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems.

Osteoarthritis and cartilage·2016
Same author

Evidence that small molecule enhancement of β-hexosaminidase activity corrects the behavioral phenotype in Dutch APP(E693Q) mice through reduction of ganglioside-bound Aβ.

Molecular psychiatry·2014
Same author

Predictive role of levels of soluble interleukin-2 receptor and C-reactive protein in selecting autologous PBSC transplantation for lymphoma.

Bone marrow transplantation·2014
Same author

Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5.

Oncogene·2014

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Alzheimer's disease (AD) is characterized by amyloid beta-protein (Abeta) deposition.
  • A novel Abeta species binding to GM1 ganglioside (GM1) in early AD brains was previously identified.
  • Abeta binding to GM1 is hypothesized to induce conformational changes, acting as a seed for aggregation.

Purpose of the Study:

  • To investigate the role of cholesterol in Abeta binding to GM1.
  • To determine if cholesterol concentration in neuronal membranes is altered by AD risk factors.
  • To examine cholesterol distribution in synaptic plasma membranes (SPMs) of human apolipoprotein E (apoE)-knock-in mice.

Main Methods:

  • Investigated the effect of increased cholesterol concentration on Abeta-GM1 binding.
  • Determined cholesterol distribution in synaptic plasma membranes (SPMs) of human apoE3 and apoE4 knock-in mice.

Main Results:

  • Increased cholesterol concentration markedly accelerates Abeta binding to GM1.
  • Cholesterol concentration in the exofacial leaflet of SPMs was approximately twice as high in human apoE4-knock-in mice compared to apoE3-knock-in mice.

Conclusions:

  • Elevated cholesterol in neuronal membranes accelerates Abeta aggregation.
  • This acceleration occurs through the formation of an endogenous Abeta-GM1-cholesterol seed.
  • The findings suggest a mechanism linking cholesterol dysregulation and apoE genotype to AD pathogenesis.

Related Experiment Videos