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

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54 Scopus citations

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, [3H]PiB binding, and soluble amyloid-β1-42 (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 [3H]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 [3H]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.

Original languageEnglish (US)
Pages (from-to)39-47
Number of pages9
JournalNeurology
Volume77
Issue number1
DOIs
StatePublished - Jul 5 2011

ASJC Scopus subject areas

  • Clinical Neurology

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    Ikonomovic, M. D., Klunk, W. E., Abrahamson, E. E., Wuu, J., Mathis, C. A., Scheff, S. W., Mufson, E. J., & DeKosky, S. T. (2011). Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease. Neurology, 77(1), 39-47. https://doi.org/10.1212/WNL.0b013e3182231419