Journal of Alzheimer's Disease - Volume 16, issue 3

Authors: Jackisch, Rolf | Förster, Stefan | Kammerer, Miriam | Rothmaier, Anna K. | Ehret, Andreas | Zentner, Josef | Feuerstein, Thomas J.

Article Type: Research Article

Abstract: Fresh specimens of human and rat neocortex were used to determine direct and indirect inhibitory potencies of choline esterase inhibitors (ChEIs) on ChE and the release of acetylcholine (ACh), respectively. Km values of ChE in homogenates of rat and human neocortex did not differ significantly, whereas the specific activity of ChE was > times higher in the rat. Butyryl ChE exhibited a higher Km and a lower specific activity than ACh esterase in human neocortex. Inhibition of ChE in rat and human tissue was similar [IC50 (nM; human): donepezil: 14, physostigmine: 22, tacrine: 95, galanthamine: 575, rivastigmine: …9120]. In neocortex slices preincubated with [3 H]choline, the electrically evoked release of [3 H]ACh was inhibited up to 60% by ChEIs (IC50 (nM, rat): donepezil: 30, physostigmine: 39, tacrine: 302, galanthamine: 646, rivastigmine: >10000). Similar IC50 -values were also estimated for ACh release in human neocortex, although the maximal inhibitory effects were much smaller (∼20%). We conclude that in comparison to rats: 1) neocortical ChE concentrations are lower and 2) that ChEIs have weaker indirect (muscarine receptor-mediated) presynaptic inhibitory effects in the human brain. We further suggest that a combination of ChEIs with brain-selective muscarine autoreceptor antagonists might help to improve their clinical efficacy. Show more

Keywords: Acetylcholine esterase, acetylcholine release, donepezil, galanthamine, physostigmine, rivastigmine, tacrine

DOI: 10.3233/JAD-2009-1008

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 635-647, 2009

Authors: Leyhe, Thomas | Eschweiler, Gerhard W. | Stransky, Elke | Gasser, Thomas | Annas, Peter | Basun, Hans | Laske, Christoph

Article Type: Research Article

Abstract: Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimer's disease (AD). In experimental investigations, lithium induces brain-derived neurotrophic factor (BDNF). Recent studies have found a decrease of BDNF in the serum and brains of AD patients with potentially consecutive lack of neurotrophic support. We assessed the influence of a lithium treatment on BDNF serum concentration in a subset of a greater sample recruited for a randomized, single-blinded, placebo-controlled, parallel-group multicenter 10-week study, investigating the efficacy of lithium treatment in AD patients. In AD patients treated with lithium, a significant increase of BDNF serum …levels, and additionally a significant decrease of ADAS-Cog sum scores in comparison to placebo-treated patients, were found. Diminution of cognitive impairment was inversely correlated with lithium serum concentration. Upregulation of BDNF might be part of a neuroprotective effect of lithium in AD patients. The results of the present investigation encourage performing studies with longer treatment phases to observe potential positive long-term effects of lithium in AD patients. Show more

Keywords: Alzheimer's disease, brain-derived neurotrophic factor, lithium, neuroprotection, neurotrophic effect, placebo-controlled trial

DOI: 10.3233/JAD-2009-1004

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 649-656, 2009

Article Type: Discussion

DOI: 10.3233/JAD-2009-1014

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 657-666, 2009

Article Type: Correction

DOI: 10.3233/JAD-2009-1064

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 667-668, 2009

Article Type: Announcement

DOI: 10.3233/JAD-2009-1028

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 669-671, 2009