LVR-Klinikum Düsseldorf Hospital of the Heinrich-Heine University ...

predisposition factors, which affect the biochemical
characteristics of nicotinic acetylcholine receptors (nAchR),
could underlie this comorbidity of schizophrenia and nicotine
dependence. The aim of our investigation is, therefore,
to characterise the expression and regulation of nAChR
subtypes, which have already been associated with the
pathogenesis of nicotine dependence (alpha4/beta2) and
schizophrenia (alpha7, alpha4/beta2). As an experimental
investigation model, B-lymphoblast lines of mentally healthy
individuals as well as of smokers and non-smokers with
schizophrenia were established. The B-lymphoblast model
we established earlier for other research questions allows
the quantification and characterisation of cell receptors
(here, nicotinic acetylcholine receptors) under standardised,
experimental conditions ex vivo (Figures 7 and 8). Directly
effective regulatory influences, such as high nicotine
consumption and endocrine or immunological infections,
can be excluded as irrelevant, although outlasting cellular
biological characteristics of the individual organism of origin
of the cultivated cells could, as an “imprint”, affect the
cellular regulation of receptors and be preserved as a trait
characteristic in vitro.
The development and validation of cerebrospinal fluid
(CSF)-based biomarkers for Alzheimer’s Dementia
C. Luckhaus, K. Fehsel in cooperation with AG Wiltfang
within the FMER –funded Competence Network on Dementia
Project period: from 2005
Financing: Sub-project within the FMER-funded
Competence Network on Dementia (Funding No: 01GI0420)
Molecular correlates of central pathogenetic processes
of Alzheimer’s Dementia, such as hyperphosphorylated
tau protein and beta amyloid, are suitable early diagnosis
markers in the CSF and, possibly, also in the blood. In
cooperation with J. Wiltfang’s group within the Competence
Network on Dementia, various aspects of the development
of biomarkers were analysed, such as the optimisation of
measurement procedures (multi-analyte profiling [Luminex]
technique), establishing combinations of biomarkers (e.g.
betaA1-42/betaA1-40 ratio) and comparative investigations
in the blood and CSF compartments. The aim of this project
was to establish the best possible diagnostic markers for
Alzheimer’s Dementia for clinical use.
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80
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Figure 7: Specific binding of radioactive nicotine to
B-lymphoblasts; figure modified after Ferrea S, Henning
U, Luckhaus C (2008). B-lymphoblasts as an in vitro model
for the study of nicotinic acetylcholine receptor regulation
in schizophrenics in relation to nicotine abuse. Int J
Neuropsychopharmacol 11 (Suppl.1): 260. Abstract
Nicotine acetylcholine receptors (fmol/10 cells)
4,0
3,5
3,0
2,5
2,0
1,5
1,0
0,5
a) b) c) d)
ReseaRch
Spec. binding in 1.2 million cells (radioactive count rate, dots per minute)
Spec. binding in 2.4 million cells (radioactive count rate, dots per minute)
0
0.0 0.4 0.8 1.2
H-nicotine concentration (nM/L)
(*p =0.006) (p = 0.071) (p = 0.182) *p = 0.046)
0,0 (-) (+) (-) (+) (-) (+) (-) (+)
Control persons Schizophrenia Control Schizophrenia
Smoker Non-smoker
Figure 8: Scattergramm of the binding of H nicotine to B-Lymphoblasts,
after long-term incubation with nicotine, in healthy and control persons
with schizophrenia. Modified after Ferrea S, Henning U, Luckhaus C (2008).
B lymphoblasts as an in vitro model for the study of nicotinic acetylcholine
receptor regulation in schizophrenics in relation to nicotine abuse. Int J
Neuropsychopharmacol 11 (Suppl.1): 260. Abstract
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