Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine.

Hans Basun, Camilla Nilsberth, Christopher Eckman, Lars Lannfelt, Steven G Younkin

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid beta-peptide (Abeta) is considered to be a key pathogenic event in Alzheimer's disease (AD). It has been suggested that stimulation of the muscarinic M(1) receptor subtype affects APP processing and leads to a change in Abeta concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Abeta in plasma, we measured Abeta42 and Abeta40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Abeta42 and Abeta40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Abeta42 and Abeta40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Abeta42 (r = -0.64; p = 0.01) and Abeta40 (r = -0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Abeta42 (r = 0.33; p = 0.34) or Abeta40 (r = -0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower beta-amyloid levels. This might indicate an effect on APP metabolism with an increased alpha-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on beta-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.

Original languageEnglish (US)
Pages (from-to)156-160
Number of pages5
JournalDementia and Geriatric Cognitive Disorders
Volume14
Issue number3
StatePublished - 2002
Externally publishedYes

Fingerprint

Tacrine
Cholinesterase Inhibitors
Amyloid beta-Protein Precursor
Amyloid beta-Peptides
Alzheimer Disease
Amyloid
Therapeutics
Pharmaceutical Preparations
Acetylcholinesterase
Cholinergic Agents

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Neuropsychology and Physiological Psychology

Cite this

Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine. / Basun, Hans; Nilsberth, Camilla; Eckman, Christopher; Lannfelt, Lars; Younkin, Steven G.

In: Dementia and Geriatric Cognitive Disorders, Vol. 14, No. 3, 2002, p. 156-160.

Research output: Contribution to journalArticle

@article{75d922542f1a444d9628350d296b8dc1,
title = "Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine.",
abstract = "Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid beta-peptide (Abeta) is considered to be a key pathogenic event in Alzheimer's disease (AD). It has been suggested that stimulation of the muscarinic M(1) receptor subtype affects APP processing and leads to a change in Abeta concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Abeta in plasma, we measured Abeta42 and Abeta40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Abeta42 and Abeta40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Abeta42 and Abeta40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Abeta42 (r = -0.64; p = 0.01) and Abeta40 (r = -0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Abeta42 (r = 0.33; p = 0.34) or Abeta40 (r = -0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower beta-amyloid levels. This might indicate an effect on APP metabolism with an increased alpha-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on beta-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.",
author = "Hans Basun and Camilla Nilsberth and Christopher Eckman and Lars Lannfelt and Younkin, {Steven G}",
year = "2002",
language = "English (US)",
volume = "14",
pages = "156--160",
journal = "Dementia and Geriatric Cognitive Disorders",
issn = "1420-8008",
publisher = "S. Karger AG",
number = "3",

}

TY - JOUR

T1 - Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine.

AU - Basun, Hans

AU - Nilsberth, Camilla

AU - Eckman, Christopher

AU - Lannfelt, Lars

AU - Younkin, Steven G

PY - 2002

Y1 - 2002

N2 - Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid beta-peptide (Abeta) is considered to be a key pathogenic event in Alzheimer's disease (AD). It has been suggested that stimulation of the muscarinic M(1) receptor subtype affects APP processing and leads to a change in Abeta concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Abeta in plasma, we measured Abeta42 and Abeta40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Abeta42 and Abeta40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Abeta42 and Abeta40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Abeta42 (r = -0.64; p = 0.01) and Abeta40 (r = -0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Abeta42 (r = 0.33; p = 0.34) or Abeta40 (r = -0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower beta-amyloid levels. This might indicate an effect on APP metabolism with an increased alpha-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on beta-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.

AB - Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid beta-peptide (Abeta) is considered to be a key pathogenic event in Alzheimer's disease (AD). It has been suggested that stimulation of the muscarinic M(1) receptor subtype affects APP processing and leads to a change in Abeta concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Abeta in plasma, we measured Abeta42 and Abeta40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Abeta42 and Abeta40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Abeta42 and Abeta40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Abeta42 (r = -0.64; p = 0.01) and Abeta40 (r = -0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Abeta42 (r = 0.33; p = 0.34) or Abeta40 (r = -0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower beta-amyloid levels. This might indicate an effect on APP metabolism with an increased alpha-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on beta-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.

UR - http://www.scopus.com/inward/record.url?scp=0036355751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036355751&partnerID=8YFLogxK

M3 - Article

C2 - 12218259

AN - SCOPUS:0036355751

VL - 14

SP - 156

EP - 160

JO - Dementia and Geriatric Cognitive Disorders

JF - Dementia and Geriatric Cognitive Disorders

SN - 1420-8008

IS - 3

ER -