title: Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease.
abstract: OBJECTIVE
  This study examined the relationship between postmortem precuneus cholinergic enzyme activity, Pittsburgh compound B (PiB) binding, and soluble amyloid-β concentration in mild cognitive impairment (MCI) and Alzheimer disease (AD).
  
  
  METHODS
  Choline acetyltransferase (ChAT) activity, [(3)H]PiB binding, and soluble amyloid-β(1-42) (Aβ42) concentration were quantified in precuneus tissue samples harvested postmortem from subjects with no cognitive impairment (NCI), MCI, and mild AD and correlated with their last antemortem Mini-Mental State Examination (MMSE) score and postmortem pathologic evaluation according to the National Institute on Aging-Reagan criteria, recommendations of the Consortium to Establish a Registry for Alzheimer's Disease, and Braak stage.
  
  
  RESULTS
  Precuneus ChAT activity was lower in AD than in NCI and was comparable between MCI and NCI. Precuneus [(3)H]PiB binding and soluble Aβ42 levels were elevated in MCI and significantly higher in AD than in NCI. Across all case subjects, reduced ChAT activity was associated with increased [(3)H]PiB binding, increased soluble Aβ42, lower MMSE score, presence of the APOE*4 allele, and more advanced AD pathology.
  
  
  CONCLUSIONS
  Despite accumulating amyloid burden, cholinergic enzyme activity is stable in the precuneus during prodromal AD. A decline in precuneus ChAT activity occurs only in clinical AD, when PiB binding and soluble Aβ42 levels are substantially elevated compared with those in MCI. Anti-amyloid interventions in MCI case subjects with a positive PiB PET scan may aid in reducing cholinergic deficits and cognitive decline later in the disease process.
authors.affiliation: Department of Neurology, University of Pittsburgh, 200 Lothrop Street BST S521, Pittsburgh, PA 15213, USA. ikonomovicmd@upmc.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Ikonomovic
authors.forename: W E
authors.initials: WE
authors.lastname: Klunk
authors.forename: E E
authors.initials: EE
authors.lastname: Abrahamson
authors.forename: J
authors.initials: J
authors.lastname: Wuu
authors.forename: C A
authors.initials: CA
authors.lastname: Mathis
authors.forename: S W
authors.initials: SW
authors.lastname: Scheff
authors.forename: E J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: S T
authors.initials: ST
authors.lastname: DeKosky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000493:pharmacokinetics; D016022:Case-Control Studies; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011180:Postmortem Changes; D011569:Psychiatric Status Rating Scales; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D013844:Thiazoles; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D014316:Tritium; D002795:Choline O-Acetyltransferase