A distinct subfraction of Aß is responsible for the high-affinity Pittsburgh compound B-binding site in Alzheimer's disease brain.
J Neurochem
; 131(3): 356-68, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-24995708
ABSTRACT
The positron emission tomography (PET) ligand (11) C-labeled Pittsburgh compound B (PIB) is used to image ß-amyloid (Aß) deposits in the brains of living subjects with the intent of detecting early stages of Alzheimer's disease (AD). However, deposits of human-sequence Aß in amyloid precursor protein transgenic mice and non-human primates bind very little PIB. The high stoichiometry of PIBAß 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 Aß 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 gangliosideAß 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 Aß 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 Aß 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiazoles
/
Química Encefálica
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Péptidos beta-Amiloides
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Enfermedad de Alzheimer
/
Compuestos de Anilina
Límite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
J Neurochem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos