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- Basun, H, et al.
(författare)
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Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine
- 2002
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:3, s. 156-160
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Tidskriftsartikel (refereegranskat)abstract
- Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid β-peptide (Aβ) is considered to be a key pathogenic event in Alzheimer’s disease (AD). It has been suggested that stimulation of the muscarinic M<sub>1</sub> receptor subtype affects APP processing and leads to a change in Aβ concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Aβ in plasma, we measured Aβ42 and Aβ40 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 Aβ42 and Aβ40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Aβ42 and Aβ40 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 Aβ42 (r = –0.64; p = 0.01) and Aβ40 (r = –0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Aβ42 (r = 0.33; p = 0.34) or Aβ40 (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 β-amyloid levels. This might indicate an effect on APP metabolism with an increased α-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on β-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.
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