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We studied the ability of four non-conjugated α7-subunit fragments of the nicotinic acetylcholine receptor to induce an immune response and to protect memory in olfactory bulbectomized mice which demonstrate abnormalities similar to Alzheimer's disease (AD). Vaccination only with the α7-subunit fragment 173–193 was shown to rescue spatial memory, to restore the level of α7 acetylcholine receptors in the cortex, and to prevent an increase in the amyloid-β (Aβ) level in brain tissue in these animals. Antibodies against the peptide 173–193 were revealed in blood serum and cerebrospinal liquid in the bulbectomized mice. Passive immunization with mouse blood sera containing antibodies to the peptide 173–193 also restored memory in bulbectomized animals. The observed positive effect of both active and passive immunization with the fragment of α7-subunit on memory of bulbectomized mice provides a new insight into an anti-AD drug design. [ABSTRACT FROM AUTHOR]

Abstract: Alterations in electroencephalogram (EEG) asymmetry and deficits in interhemispheric integration of information have been shown in patients with Alzheimer''s disease (AD). However, no direct evidence of an association between EEG asymmetry, morphological markers in the brain, and cognition was found either in AD patients or in AD models. In this study we used rats with bilateral olfactory bulbectomy (OBX) as one of the AD models and measured their learning/memory abilities, brain beta-amyloid levels and EEG spectra in symmetrical frontal and occipital cortices. One year after OBX or sham-surgery, the rats were tested with the Morris water paradigm and assigned to three groups: sham-operated rats, SO, and OBX rats with virtually normal, OBX(+), or abnormal, OBX(−), learning (memory) abilities. In OBX vs. SO, the theta EEG activity was enhanced to a higher extent in the right frontal cortex and in the left occipital cortex. This produced significant interhemispheric differences in the frontal cortex of the OBX(−) rats and in the occipital cortex of both OBX groups. The beta1 EEG asymmetry in SO was attenuated in OBX(+) and completely eliminated in OBX(−). OBX produced highly significant beta2 EEG decline in the right frontal cortex, with OBX(−)>OBX(+) rank order of strength. The beta-amyloid level, examined by post-mortem immunological DOT-analysis in the cortex–hippocampus samples, was about six-fold higher in OBX(−) than in SO, but significantly less (enhanced by 82% vs. SO) in OBX(+) than in OBX(−). The involvement of the brain mediatory systems in the observed EEG asymmetry differences is discussed. [Copyright &y& Elsevier]