Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer’s disease

Parnetti, Lucilla; Chiasserini, Davide; Andréasson, Ulf; Ohlson, Mats; Huls, Chris; Zetterberg, Henrik; Minthon, Lennart; Wallin, Åsa; Andreasen, Niels; Talesa, Vincenzo Nicola; Blennow, Kaj

doi:10.1111/j.1600-0404.2010.01435.x

Cited by 34 publications

(26 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This relationship is perhaps counter-intuitive, given that the goal of ChE-I treatment is to dampen AChE activity and thus enhance cholinergic transmission. However, our results are consistent with previous studies which reported increased AChE activity in plasma and CSF among AD patients who were treated with donepezil (22, 46-48). It is possible that suppression of ChE activity in AD patients is transient, and that treatment may lead to a “rebound” of activity via compensatory mechanisms (49), perhaps explaining the apparently transient benefit of ChE-I treatment (50).…”

Section: Discussionsupporting

confidence: 93%

Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load

Alkalay¹,

Rabinovici²,

Zimmerman³

et al. 2013

Current Alzheimer Research

View full text Add to dashboard Cite

Background Previous studies have demonstrated alterations in the peripheral cholinergic system in Alzheimer’s disease (AD), though results have been inconsistent and not linked to in vivo biomarkers of pathology. We examined the relationship between amyloid-beta (Aβ) plaques and plasma cholinesterase activity in a heterogeneous dementia population. Methods 29 participants with clinical AD and 35 with non-AD diagnoses underwent positron emission tomography (PET) with the amyloid ligand [11C] PIB and plasma measurements of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Multi-linear regression was used to evaluate the relationship between AChE or BChE activity and PIB binding (adjusted for age, sex, apolipoprotein E4 and vascular risk), applying voxel-wise and region of interest (ROI) approaches. AChE activity was further adjusted for cholinesterase inhibitor (ChE-I) use. Global amyloid load was measured using a PIB Index, representing mean tracer binding in frontal, parietal, lateral temporal and cingulate cortex. Results AChE activity was correlated with PIB Index (β=0.39, p<0.001) and with regional PIB binding in frontal, temporal, parietal and occipital lobes, precuneus and posterior cingulate on both voxel-wise (p<0.001 uncorrected) and ROI (β=0.26-0.41, p<0.005) analysis. Correlations remained significant after covarying clinical diagnosis (β=0.42, p=0.001), and among participants naive to ChE-I (β=0.51, p=0.005). No correlation was found between BChE activity and PIB. Among AD participants, disease severity was not correlated with AChE, BChE or PIB Index. Conclusion AChE activity in plasma is correlated with brain Aβ load. Activation of the ‘anti-inflammatory cholinergic pathway’ may provide the link between Aβ plaques and peripheral cholinergic measures.

show abstract

Section: Discussionsupporting

confidence: 93%

Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load

Alkalay¹,

Rabinovici²,

Zimmerman³

et al. 2013

Current Alzheimer Research

View full text Add to dashboard Cite

show abstract

“…Moreover, a 13-week, randomized, open-label study56 in patients with mild-to-moderate AD showed that rivastigmine significantly decreased activity of both AChE and BuChE in the CSF by 42.6% ( P <0.001 vs baseline; AChE protein levels decreased by 21.8%) and 45.4% ( P <0.001 vs baseline; BuChE protein levels decreased by 9.3%), respectively, whereas donepezil and galantamine did not significantly decrease BuChE activity, and these enzymes were associated with increased levels of cholinesterases in the CSF. Similarly, results from a clinical study57 in patients with probable AD showed that rivastigmine treatment decreased CSF AChE and BuChE activity and was statistically significant in only rivastigmine 12 mg/day group ( P <0.01) as there were fewer patients in the 6 and 9 mg/day groups; however, treatment with donepezil ( P <0.0001) and galantamine ( P <0.001) showed significant increase in CSF AChE activity, but no change in BuChE activity was observed. The change in CSF AChE activity with donepezil treatment was dose related (mean percentage change with 5 and 10 mg/day: +88% and +116%, respectively), and the percentage change in CSF AChE activity was significantly different between the two doses ( P <0.01), whereas the change in CSF AChE activity with galantamine was not dose related (8 and 12 mg/day: +53% and +52%, respectively).…”

Section: Rivastigmine: Dual Inhibitor Ache/buchementioning

confidence: 94%

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

Kandiah¹,

Pai²,

Senanarong³

et al. 2017

CIA

161

View full text Add to dashboard Cite

Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE−BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

show abstract

“…CSF concentrations of PTH were below the lower detection limit of the assay (3 ng/L). CSF AChE and BuChE activities were determined using in house assays as previously described in detail [25]. …”

Section: Methodsmentioning

confidence: 99%

Cerebrospinal Fluid (CSF) 25-Hydroxyvitamin D Concentration and CSF Acetylcholinesterase Activity Are Reduced in Patients with Alzheimer's Disease

et al. 2013

View full text Add to dashboard Cite

BackgroundLittle is known of vitamin D concentration in cerebrospinal fluid (CSF) in Alzheimer´s disease (AD) and its relation with CSF acetylcholinesterase (AChE) activity, a marker of cholinergic function.MethodsA cross-sectional study of 52 consecutive patients under primary evaluation of cognitive impairment and 17 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 28), other dementias (n = 12), and stable MCI (SMCI, n = 12). We determined serum and CSF concentrations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and CSF activities of AChE and butyrylcholinesterase (BuChE). FindingsCSF 25OHD level was reduced in AD patients (P < 0.05), and CSF AChE activity was decreased both in patients with AD (P < 0.05) and other dementias (P < 0.01) compared to healthy controls. None of the measured variables differed between BuChE K-variant genotypes whereas the participants that were homozygous in terms of the apolipoprotein E (APOE) ε4 allele had decreased CSF AChE activity compared to subjects lacking the APOE ε4 allele (P = 0.01). In AD patients (n=28), CSF AChE activity correlated positively with CSF levels of total tau (T-tau) (r = 0.44, P < 0.05) and phosphorylated tau protein (P-tau) (r = 0.50, P < 0.01), but CSF activities of AChE or BuChE did not correlate with serum or CSF levels of 25OHD.ConclusionsIn this pilot study, both CSF 25OHD level and CSF AChE activity were reduced in AD patients. However, the lack of correlations between 25OHD levels and CSF activities of AChE or BuChE might suggest different mechanisms of action, which could have implications for treatment trials.

show abstract

Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer’s disease

Abstract: AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.

Cited by 34 publications

References 36 publications

Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load

Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

Cerebrospinal Fluid (CSF) 25-Hydroxyvitamin D Concentration and CSF Acetylcholinesterase Activity Are Reduced in Patients with Alzheimer's Disease

Contact Info

Product

Resources

About

Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer’s disease

Abstract: AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.

Cited by 34 publications

References 36 publications

Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load

Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson&rsquo;s disease dementia

Cerebrospinal Fluid (CSF) 25-Hydroxyvitamin D Concentration and CSF Acetylcholinesterase Activity Are Reduced in Patients with Alzheimer's Disease

Contact Info

Product

Resources

About

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia