University of Virginia

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease.

M D Ikonomovic; W E Klunk; E E Abrahamson; J Wuu; C A Mathis; S W Scheff; E J Mufson; S T DeKosky (Profiled Authors: Mufson, Elliott J; DeKosky, Steven T)

Department of Neurology, University of Pittsburgh, 200 Lothrop Street BST S521, Pittsburgh, PA 15213, USA. ikonomovicmd@upmc.edu
Neurology 2011;77(1):39-47.

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.

4 Originating Grant

• 1.

  Dekosky, Steven T

  In VivoPIB PET Amyloid Imaging: Normals, MCI & Dementia

  15 May 2005 - 30 April 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 2,947,677

• 2.

  MUFSON, ELLIOTT JAY

  Neurobiology of Mild Cognitive Impairment in the Elderly

  1 September 1997 - 31 March 2013

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 20,516,366

• 3.

  BENNETT, DAVID ALAN

  Rush Alzheimer's Disease Core Center

  15 August 1997 - 30 June 2016

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 20,028,581

• 4.

  Dekosky, Steven T

  Alzheimer's DIsease Research Center

  1 May 1997 - 31 March 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 23,347,917

Scientific Context

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