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Neurology. 2011 Jul 5;77(1):39-47. doi: 10.1212/WNL.0b013e3182231419. Epub 2011 Jun 22.

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

Author information

1
Department of Neurology, University of Pittsburgh, 200 Lothrop Street BST S521, Pittsburgh, PA 15213, USA. ikonomovicmd@upmc.edu

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.

PMID:
21700583
PMCID:
PMC3127332
DOI:
10.1212/WNL.0b013e3182231419
[Indexed for MEDLINE]
Free PMC Article

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