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

Cholinergic deficit associated with loss of nicotinic acetylcholine recepto rs (nAChRs) has been described in Alzheimer's disease (AD) by receptor bind ing assays, positron emission tomography and immunoblotting. However, littl e is known about the alteration of these receptors in a related disease, Do wn syndrome (DS) which might be of importance for therapeutic strategies. T he protein levels of neuronal nAChR alpha and beta subunits in human postmo rtem brain samples (frontal cortex and cerebellum) of control, adult DS, an d AD were investigated by making use of western blot analysis. Two major bands at 26 and 45 kDa for alpha3, one at 50kDa for alpha4 and be ta2, and one at 45 kDa for alpha7 were detected by the respective antibodie s. Specific alteration in individual subunits was also apparent in DS and A D. In frontal cortex, the 45 kDa alpha3 subunit was significantly increased in DS (121 %) (P < 0.05) and AD (93%) (P < 0.05), whereas the 26kDa, an is oform/truncated form of alpha3, displayed a reversed pattern. It was signif icantly decreased in DS (75%) (P < 0.001) and AD (52.6%) (P < 0.05). alpha4 was comparable in all groups by contrast, alpha7 was significantly decreas ed in AD (64%) (P < 0.05). In DS, however, although the levels tended to be lower (17.3%) the reduction was not significant. beta2 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 subuni ts except beta2. It exhibited a significant increase (161%) (P < 0.01) in D S. Derangement in expression of nAChRs is apparent in DS, as in AD that may ha ve some relevance to DS neuropathology. Furthermore, the increase in beta2 expression indicate that these subunits may have more than a structural rol e. Hence, therapeutic strategies tailored towards these end might be of som e benefit for cognitive enhancement in these disorders.