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A distinct subfraction of Aβ is responsible for the high-affinity Pittsburgh compound B-binding site in Alzheimer's disease brain
- Source :
- Journal of Neurochemistry. 131:356-368
- Publication Year :
- 2014
- Publisher :
- Wiley, 2014.
-
Abstract
- The positron emission tomography (PET) ligand (11) C-labeled Pittsburgh compound B (PIB) is used to image β-amyloid (Aβ) deposits in the brains of living subjects with the intent of detecting early stages of Alzheimer's disease (AD). However, deposits of human-sequence Aβ in amyloid precursor protein transgenic mice and non-human primates bind very little PIB. The high stoichiometry of PIB:Aβ binding in human AD suggests that the PIB-binding site may represent a particularly pathogenic entity and/or report local pathologic conditions. In this study, (3) H-PIB was employed to track purification of the PIB-binding site in > 90% yield from frontal cortical tissue of autopsy-diagnosed AD subjects. The purified PIB-binding site comprises a distinct, highly insoluble subfraction of the Aβ in AD brain with low buoyant density because of the sodium dodecyl sulfate-resistant association with a limited subset of brain proteins and lipids with physical properties similar to lipid rafts and to a ganglioside:Aβ complex in AD and Down syndrome brain. Both the protein and lipid components are required for PIB binding. Elucidation of human-specific biological components and pathways will be important in guiding improvement of the animal models for AD and in identifying new potential therapeutic avenues. A lipid-associated subpopulation of Aβ accounts for the high-affinity binding of Pittsburgh compound B (PIB) in Alzheimer's disease brain. Mass spectrometry of the isolated PIB-binding site from frontal cortex identified Aβ peptides and a set of plaque-associated proteins in AD but not age-matched normal brain. The PIB-binding site may represent a particularly pathogenic entity and/or report local pathologic conditions.
- Subjects :
- Male
Proteomics
Amyloid
In Vitro Techniques
Biochemistry
Article
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Alzheimer Disease
medicine
Amyloid precursor protein
Humans
Binding site
Lipid raft
Aged
Aged, 80 and over
Brain Chemistry
Amyloid beta-Peptides
Aniline Compounds
Binding Sites
Ganglioside
biology
Lipid Metabolism
medicine.disease
Ligand (biochemistry)
Frontal Lobe
Thiazoles
chemistry
biology.protein
Female
Down Syndrome
Alzheimer's disease
Pittsburgh compound B
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi.dedup.....8000e0d8e89e58040c184d22ca1c5d01