title: Decreased clearance of CNS beta-amyloid in Alzheimer's disease.
abstract: Alzheimer's disease is hypothesized to be caused by an imbalance between β-amyloid (Aβ) production and clearance that leads to Aβ accumulation in the central nervous system (CNS). Aβ production and clearance are key targets in the development of disease-modifying therapeutic agents for Alzheimer's disease. However, there has not been direct evidence of altered Aβ production or clearance in Alzheimer's disease. By using metabolic labeling, we measured Aβ42 and Aβ40 production and clearance rates in the CNS of participants with Alzheimer's disease and cognitively normal controls. Clearance rates for both Aβ42 and Aβ40 were impaired in Alzheimer's disease compared with controls. On average, there were no differences in Aβ40 or Aβ42 production rates. Thus, the common late-onset form of Alzheimer's disease is characterized by an overall impairment in Aβ clearance.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kwasi G
authors.initials: KG
authors.lastname: Mawuenyega
authors.forename: Wendy
authors.initials: W
authors.lastname: Sigurdson
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Ovod
authors.forename: Ling
authors.initials: L
authors.lastname: Munsell
authors.forename: Tom
authors.initials: T
authors.lastname: Kasten
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Yarasheski
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)