Butyrylcholinesterase and progression of cognitive deficits in dementia with Lewy bodies

Perry, Elaine K.; McKeith, Ian G.; Ballard, Clive

doi:10.1212/01.wnl.0000068336.84399.9e

Cited by 61 publications

(40 citation statements)

References 8 publications

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“…In patients with dementia, BChE variants correlated with a preserved attentional performance and a reduced rate of cognitive decline (42,43). Also, in Lewy body dementia, where the cholinergic deficit is considered more profound than in AD (44), a prospectively designed study of autopsy-confirmed cases showed a highly significant association between lower activity of BChE in the temporal cortex and a slower rate of cognitive decline (45).…”

Section: Discussionmentioning

confidence: 99%

Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent

Greig

Utsuki

Ingram

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

653

433

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Like acetylcholinesterase , butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused longterm inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE inhibition augmented long-term potentiation. These compounds also improved the cognitive performance (maze navigation) of aged rats. In cultured human SK-N-SH neuroblastoma cells, intra-and extracellular ␤-amyloid precursor protein, and secreted ␤-amyloid peptide levels were reduced without affecting cell viability. Treatment of transgenic mice that overexpressed human mutant amyloid precursor protein also resulted in lower ␤-amyloid peptide brain levels than controls. Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease.anticholinesterase ͉ long-term potentiation ͉ dementia ͉ memory ͉ neurodegeneration

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Section: Discussionmentioning

confidence: 99%

Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent

Greig

Utsuki

Ingram

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

653

433

View full text Add to dashboard Cite

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“…67 An earlier neuropathological study in subjects with dementia with Lewy bodies, not AD, showed a significant correlation between BuChE activity in the temporal cortex at post mortem and more rapid cognitive decline during life, which was independent of disease severity, duration and age. 33 Moreover, in a predominantly dementia with Lewy bodies cohort, the BCHE-K variant is associated with enhanced attention at baseline and poorer response to rivastigmine treatment, compared with those who did not carry the K variant and had impaired attention at baseline. 32 Disease progression in those with the K variant was only 60% of that seen in the wild-type group.…”

Section: Apoe Bche and Chei Treatment Response In Admentioning

confidence: 98%

“…31 Homozygous individuals have approximately 30% reduced plasma BuChE activity 31 and show a slower rate of cognitive decline. 32,33 Lehmann et al 34 published the initial report of an association of BCHE-K with increased risk of AD. Several groups, including our own, 35 independently replicated this association.…”

Section: Introductionmentioning

confidence: 99%

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

2010

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“…The protein, BCHE, is an acetylcholine-hydrolyzing enzyme. BCHE is considered to be relevant to the progressive memory disorder and dementia in AD (22,23) and has been associated with NFTs and Aβ in the pathology of AD (24). In addition, BCHE has been found to play an important role in AD plaque maturation (25).…”

Section: Introductionmentioning

confidence: 99%

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

Dai

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with β-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date.

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Butyrylcholinesterase and progression of cognitive deficits in dementia with Lewy bodies

Cited by 61 publications

References 8 publications

Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent

Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

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