Background: Adiponectin and leptin are implicated in the initiation and pathomechanism of Alzheimer’s disease (AD). The serum concentrations of these adipokines has been extensively studied in AD, however little is known about their receptors in this disease. Objective: We developed a novel approach to examine whether the receptors of adiponectin (AdipoR1 and -R2) and/or leptin (LepR) can contribute to AD pathomechanism. To achieve this, we investigated the effect of both genetic and environmental factors associated with AD on the expression of these receptors. Method: We used C57BL/6J (WT) and APP(swe)/Presen(e9d)1 (AD) mice. Both strains were exposed to restraint stress (RS) daily for 6h over different time periods. Then, we measured the mRNA expression of AdipoR1, AdipoR2 and LepR and the level of AdipoR1 and AdipoR2 proteins in the hippocampal and prefrontal cortical areas of each mouse. Results: We detected brain region specific transcriptomic changes of adiponectin receptors induced by APP and PS1 transgenes. Both acute and chronic RS caused significant elevations in AdipoR1 mRNA expression in the hippocampus of WT mice. In the prefrontal cortex, the mRNA expression of AdipoR1 followed a biphasic course. In AD mice, RS did not promote any changes in the expression of AdipoR1 mRNA and AdipoR1 protein levels. AdipoR2 mRNA in AD animals, however, showed a significant increase in the prefrontal cortex during RS. Regarding AdipoR1 and AdipoR2 mRNA and protein expression, relevant changes could be measured during stress exposure in both brain areas. Furthermore, stress exposed groups exhibited little change in LepR mRNA expression. Conclusion: Our findings indicate that carrying the transgenes associated with AD induces modification in the expression of both adiponectin receptors. In the case of a normal genetic background, these receptors also appear to be sensitive to environmental factors, while in a genetically determined AD model less response to stress stimuli could be observed. The results suggest that modification of adipokine receptors could also be considered in the therapeutic approach to AD.

Calcium homeostasis modulator 1 (CALHM1), a promising candidate gene for Alzheimer's disease risk, has been recently identified. We tested the hypothesis that the T-allelic variant of the CALHM1 rs2986017 polymorphism confers susceptibility to Alzheimer's disease in a Hungarian case–control sample that was also genotyped for apolipoprotein E. This study included 238 probable patients with Alzheimer's disease who met the diagnostic criteria for National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and 202 elderly healthy control participants. We failed to detect an association between the CALHM1 polymorphism and the risk for Alzheimer's disease (P=0.153 for genotypes and P=0.090 for alleles), nor did we find an effect on age at onset. However, a potential weak correlation between the presence of the T allele (CT and TT genotypestogether) and Alzheimer's disease was observed (P=0.056).

Damage to and functional alteration of structures responsible for synaptic plasticity correlate with memory loss and cognitive decline in Alzheimer's disease. The results of recent research in the pathomechanism of Alzheimer's disease emphasize the significance of cytoskeletal changes. The changes in actin dynamics and its regulation by actin-binding proteins have been proven in Alzheimer's disease, which may have a key role in the conformation and alteration of synapses and dendritic spines. The most important proteins in the regulation of actin dynamics are ADF/cofilin, kinases and drebrin. In this review, we summarize the physiological functions and complex regulation of these cytoskeletal proteins and their alterations in Alzheimer's disease. Additionally, the effects of some psychopharmacons on the actin cytoskeleton and cytoskeletal changes induced by stress are also summarized.