Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer’s disease

  • E. Engidawork
  • T. Gulesserian
  • N. Balic
  • N. Cairns
  • G. Lubec


Cholinergic deficit associated with loss of nicotinic acetylcholine receptors (nAChRs) has been described in Alzheimer’s disease (AD) by receptor binding assays, positron emission tomography and immunoblotting. However, little is known about the alteration of these receptors in a related disease, Down syndrome (DS) which might be of importance for therapeutic strategies. The protein levels of neuronal nAChR alpha and beta subunits in human postmortem brain samples (frontal cortex and cerebellum) of control, adult DS, and AD were investigated by making use of western blot analysis.

Two major bands at 26 and 45 kDa for α3, one at 50 kDa for α4 and ß2, and one at 45 kDa for α7 were detected by the respective antibodies. Specific alteration in individual subunits was also apparent in DS and AD. In frontal cortex, the 45 kDa α3 subunit was significantly increased in DS (121%) (P < 0.05) and AD (93%) (P < 0.05), whereas the 26kDa, an isoform/truncated form of a3, displayed a reversed pattern. It was significantly decreased in DS (75%) (P < 0.001) and AD (52.6%) (P < 0.05). a4 was comparable in all groups by contrast,α7 was significantly decreased in AD (64%) (P < 0.05). In DS, however, although the levels tended to be lower (17.3%) the reduction was not significant. ß2 was unchanged in AD but showed a significant increase in DS frontal cortex (98.1%) (P < 0.01). In cerebellum, no significant alteration was observed in any of the subunits except ß2. It exhibited a significant increase (161%) (P < 0.01) in DS.

Derangement in expression of nAChRs is apparent in DS, as in AD that may have some relevance to DS neuropathology. Furthermore, the increase in ß2 expression indicate that these subunits may have more than a structural role. Hence, therapeutic strategies tailored towards these end might be of some benefit for cognitive enhancement in these disorders.


Nerve Growth Factor Frontal Cortex Down Syndrome Nicotinic Acetylcholine Receptor cAMP Response Element Binding 
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Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • E. Engidawork
    • 1
  • T. Gulesserian
    • 1
  • N. Balic
    • 2
  • N. Cairns
    • 3
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Clinical Institute for Medical and Chemical Laboratory DiagnosticsViennaAustria
  3. 3.Department of Neuropathology, Institute of PsychiatryKing’s CollegeLondonUK

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