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Title: Biochemically-defined pools of amyloid-β in sporadic Alzheimer's disease: correlation with amyloid PET
Austin Authors: Roberts, Blaine R;Lind, Monica;Wagen, Aaron Z;Rembach, Alan;Frugier, Tony;Li, Qiao-Xin;Ryan, Timothy M;McLean, Catriona A;Doecke, James D;Rowe, Christopher C ;Villemagne, Victor L ;Masters, Colin L 
Affiliation: The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia
Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria, Australia
CSIRO Health and Biosecurity/Australian e-Health Research Centre and Cooperative Research Centre of Mental Health, Brisbane, QLD, Australia
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 1-May-2017
Publication information: Brain 2017; 140(5): 1486-1498
Abstract: We fractionated frontal cortical grey matter from human Alzheimer's disease and control subjects into four biochemically defined pools that represent four distinct compartments: soluble/cytosolic, peripheral membrane/vesicular cargo, integral lipid/membranous pools and aggregated/insoluble debris. Most of the readily extractable amyloid-β remains associated with a lipid/membranous compartment. There is an exchange of amyloid-β between the biochemical pools that was lost for the amyloid-β42 species in Alzheimer's disease, consistent with the peptide being irreversibly trapped in extracellular deposits. The quantitative amyloid-β data, combined with magnetic resonance imaging volumetric analysis of the amount of cortical grey matter in brain, allowed us to estimate the total mass of amyloid-β in Alzheimer's disease (6.5 mg) and control (1.7 mg) brains. The threshold positron emission tomography standard uptake value ratio of 1.4 equates to 5.0 μg amyloid-β/g of grey matter and the mean Alzheimer's disease dementia standard uptake value ratio level of 2.3 equates to 11.20 μg amyloid-β/g of grey matter. It takes 19 years to accumulate amyloid from the threshold positron emission tomography standard uptake value ratio to the mean value observed for Alzheimer's disease dementia. This accumulation time window combined with the difference of 4.8 mg of amyloid-β between Alzheimer's disease and control brain allows for a first approximation of amyloid-β accumulation of 28 ng/h. This equates to an estimated 2-5% of the total amyloid-β production being deposited as insoluble plaques. Understanding these rates of amyloid-β accumulation allows for a more quantitative approach in targeting the failure of amyloid-β clearance in sporadic Alzheimer's disease.
DOI: 10.1093/brain/awx057
ORCID: 0000-0003-3910-2453
Journal: Brain
PubMed URL:
Type: Journal Article
Subjects: Alzheimer’s disease
amyloid imaging
Appears in Collections:Journal articles

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