PMID- 17990049
OWN - NLM
STAT- MEDLINE
DCOM- 20080515
LR  - 20211020
IS  - 0940-1334 (Print)
IS  - 0940-1334 (Linking)
VI  - 258
IP  - 2
DP  - 2008 Mar
TI  - Increase of BDNF serum concentration during donepezil treatment of patients with 
      early Alzheimer's disease.
PG  - 124-8
AB  - Alzheimer's disease (AD) can be treated with inhibitors of the enzyme 
      acetylcholinesterase (AChE). Recent pre-clinical and clinical studies gave 
      evidence that AChE-inhibitors have neuroprotective effects and thereby a 
      disease-modifying potential. The mechanism of this action is still discussed. In 
      an animal model oral administration of an AChE-inhibitor lead to an increase of 
      brain derived neurotrophic factor (BDNF) in hippocampus and cortex. Recent 
      studies have found a decrease of BDNF in the serum and brain of AD patients with 
      potentially consecutive lack of neurotrophic support and contribution to 
      progressive neurodegeneration. BDNF serum concentrations were assessed by ELISA 
      in 19 AD patients and 20 age-matched healthy controls at baseline and in the AD 
      patients after 15 months of treatment with donepezil 10 mg per day (one patient 
      received just 5 mg). Before treatment with donepezil we found in AD significantly 
      decreased BDNF serum concentrations (19.2 +/- 3.7 ng/ml) as compared to healthy 
      controls (23.2 +/- 6.0 ng/ml, P = 0.015). After 15 months of treatment the BDNF 
      serum concentration increased significantly in the AD patients (23.6 +/- 7.0 
      ng/ml, P = 0.001) showing no more difference to the healthy controls (P = 0.882). 
      The results of the present study confirm data of prior investigations that a 
      down-regulation of BDNF in serum and brain of AD patients seems to begin with the 
      first clinical symptoms and to be persistent. A treatment with the AChE-inhibitor 
      donepezil is accompanied with an increase of BDNF serum concentration in AD 
      patients reaching the level of healthy controls. Thus, up-regulation of BDNF 
      might be part of a neuroprotective effect of AChE-inhibitors. The molecular 
      mechanism of this potentially disease-modifying mechanism of action of donepezil 
      should be clarified.
FAU - Leyhe, T
AU  - Leyhe T
AD  - Department of Psychiatry and Psychotherapy, University of Tubingen, 
      Osianderstrasse 24, Tubingen, Germany. thomas.leyhe@med.uni-tuebingen.de
FAU - Stransky, Elke
AU  - Stransky E
FAU - Eschweiler, G W
AU  - Eschweiler GW
FAU - Buchkremer, G
AU  - Buchkremer G
FAU - Laske, C
AU  - Laske C
LA  - eng
PT  - Controlled Clinical Trial
PT  - Journal Article
DEP - 20071107
PL  - Germany
TA  - Eur Arch Psychiatry Clin Neurosci
JT  - European archives of psychiatry and clinical neuroscience
JID - 9103030
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Indans)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*blood/drug therapy
MH  - Brain-Derived Neurotrophic Factor/*blood/drug effects
MH  - Case-Control Studies
MH  - Cholinesterase Inhibitors/*therapeutic use
MH  - Donepezil
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Indans/*therapeutic use
MH  - Male
MH  - Matched-Pair Analysis
MH  - Middle Aged
MH  - Piperidines/*therapeutic use
MH  - Up-Regulation
EDAT- 2007/11/09 09:00
MHDA- 2008/05/16 09:00
CRDT- 2007/11/09 09:00
PHST- 2007/05/15 00:00 [received]
PHST- 2007/09/11 00:00 [accepted]
PHST- 2007/11/09 09:00 [pubmed]
PHST- 2008/05/16 09:00 [medline]
PHST- 2007/11/09 09:00 [entrez]
AID - 10.1007/s00406-007-0764-9 [doi]
PST - ppublish
SO  - Eur Arch Psychiatry Clin Neurosci. 2008 Mar;258(2):124-8. doi: 
      10.1007/s00406-007-0764-9. Epub 2007 Nov 7.