In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease

  title={In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease},
  author={David Kuhl and Robert A. Koeppe and Satoshi Minoshima and Scott Snyder and E Ficaro and Normal L. Foster and Kirk A. Frey and Michael R. Kilbourn},
  pages={691 - 691}
Objective: To validate an in vivo method for mapping acetylcholinesterase (AChE) activity in human brain, preparatory to monitoring inhibitor therapy in AD. Background: AChE activity is decreased in postmortem AD brain. Lacking a reliable in vivo measure, little is known about central activity in early AD, when the disease is commonly targeted by AChE inhibitor drug therapy. Methods: Intravenous N-[11C]methylpiperidin-4-yl propionate ([11C]PMP) served as an in vivo AChE substrate. AChE activity… 

Figures and Tables from this paper

In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism
There is a global reduction of cortical AChE activity in dementia, which was reduced significantly in all brain regions in demented subjects, whereas reduction of CMRGlc and CBF was more limited to temporo-parietal association areas.
Acetylcholine esterase activity in mild cognitive impairment and Alzheimer’s disease
  • K. Herholz
  • Biology, Medicine
    European Journal of Nuclear Medicine and Molecular Imaging
  • 2007
The in vivo findings in MCI and very mild AD seem to suggest that cholinergic innervation and AChE as the main degrading enzyme are both reduced, which might result in partial compensation of their effect.
Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex
Direct positron emission tomography measures of cerebral acetylcholinesterase activity were made in AD patients before and after treatment with donepezil and compared with similar measures in normal controls who were untreated or after acute administration of another AChE inhibitor, physostigmine salicylate.
Acetate in Rats Compared With MP 4 A as a Probe for Measuring Cerebral Acetylcholinesterase Activity
The in vivo kinetics of [F]FEP-4MA would be applicable to clinical PET study for quantifying cerebral AChE activity and the responsiveness of brain uptake to A ChE activity was validated based on a mathematical model derived from the A cholinergic innervation-mediated trapping rationale.
Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease
Hippocampal acetylcholinesterase activity is only slightly reduced in mild cognitive impairment and early Alzheimer’s disease and so the value of in vivo acetylCholinestersterase measurements in detecting the early Alzheimer process is limited.
Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.
Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients, consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors.


In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease
It is concluded that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity.
Convergent cholinergic activities in aging and Alzheimer's disease
Alzheimer's disease: Choline acetyltransferase activity in brain tissue from clinical and pathological subgroups
Multivariate regression analysis showed myoclonus to be the single best predictor of low brain choline acetyltransferase activity in patients with Alzheimer's disease and a history of myOClonus.
A brain regional analysis of morphologic and cholinergic abnormalities in Alzheimer's disease.
In the brains of 21 patients with Alzheimer's disease (AD) and 10 nondemented controls, senile plaques (SPs), neurofibrillary tangles (NFTs), and three indexes of cholinergic function were quantified
Quantification of Muscarinic Cholinergic Receptors with [11C]NMPB and Positron Emission Tomography: Method Development and Differentiation of Tracer Delivery from Receptor Binding
The authors conclude that pixel-by-pixel-weighted integral analyses of NMPB distribution introduce transport biases into receptor-binding estimates, and similar confounding effects also are predicted in noncompartmental analyses of delayed radiotracer distribution.
Neurochemical correlates of major depression in primary dementia.
The results indicate that the development of major depression in primary dementia is associated with a profile of concurrent neurochemical changes that is largely consistent with existing neurochemical hypotheses of idiopathic affective disorders, and qualitatively distinct from that associated with primary dementia.
Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer's disease.
In the Lewy body cases neocortical choline acetyltransferase was consistently lower than in the classical Alzheimer's disease cases, and the combined data suggest that cholinergic therapy may be particularly relevant to patients withLewy body type dementia.
Molecular Neurobiology of Alzheimer's Disease (Syndrome?)
  • G. Zubenko
  • Psychology, Medicine
    Harvard review of psychiatry
  • 1997
The goals of this review are to cover the substantial progress that has been made over the past 5 years in the major thematic areas of research in AD and to assemble these individual findings into a more integrated picture of the pathophysiology of the disorder.
In vivo studies of acetylcholinesterase activity using a labeled substrate, N‐[11C]methylpiperdin‐4‐yl propionate ([11C]PMP)
Two esters were synthesized in no‐carrier‐added forms and evaluated as in vivo substrates for brain acetylcholinesterase (AChE) and each ester showed rapid penetration into the brain and a regional retention of radioactivity reflecting known levels of AChE activity in the brain.