Alzheimer’s disease (AD) is a neurodegenerative disease whose various pathophysiological aspects are still being investigated. Recently, it has been hypothesized that AD may be associated with a dysbiosis of microbes in the intestine. In fact, the intestinal flora is able to influence the activity of the brain and cause its dysfunctions. Given the growing interest in this topic, the purpose of this review is to analyze the role of antibiotics in relation to the gut microbiota and AD. In the first part of the review, we briefly review the role of gut microbiota in the brain and the various theories supporting the hypothesis that dysbiosis can be associated with AD pathophysiology. In the second part, we analyze the possible role of antibiotics in these events. Antibiotics are normally used to remove or prevent bacterial colonization in the human body, without targeting specific types of bacteria. As a result, broad-spectrum antibiotics can greatly affect the composition of the gut microbiota, reduce its biodiversity, and delay colonization for a long period after administration. Thus, the action of antibiotics in AD could be wide and even opposite, depending on the type of antibiotic and on the specific role of the microbiome in AD pathogenesis. Alteration of the gut microbiota can induce changes in brain activity, which raise the possibility of therapeutic manipulation of the microbiome in AD and other neurological disorders. This field of research is currently undergoing great development, but therapeutic applications are still far away. Whether a therapeutic manipulation of gut microbiota in AD could be achieved using antibiotics is still not known. The future of antibiotics in AD depends on the research progresses in the role of gut bacteria. We must first understand how and when gut bacteria act to promote AD. Once the role of gut microbiota in AD is well established, one can think to induce modifications of the gut microbiota with the use of pre-, pro-, or antibiotics to produce therapeutic effects.

Alzheimers disease (AD) is a neurodegenerative disorder characterized by cognitive decline with loss of memory. In the last years there has been a great interest on the early phases of AD, trying to identify the pathogenic mechanisms of AD and define early treatment modalities. In particular, Mild Cognitive Impairment (MCI) is attractive because it represents a transitional state between normal aging and dementia, although not all MCI patients automatically convert to AD. The neurotrophin brain-derived neurotrophic factor (BDNF) is critical for survival and function of neurons that degenerate in AD and represents a potential neuroprotective agent. However, opposite data on serum levels of BDNF have been reported in AD patients, probably reflecting differences in patient recruitment and stage of the disease. Thus, in this study we measured BDNF serum levels in AD patients (with different degree of severity), MCI patients and healthy subjects. We found that serum BNDF levels were significantly increased in MCI and AD patients when compared to healthy subjects and this increase in AD patients was neither dependent on illness severity, nor on treatment with Acetylcholinesterase inhibitors and/or antidepressant medications. Our findings indicate that BDNF serum levels increase in MCI and AD patients, supporting the hypothesis of an upregulation of BDNF in both preclinical phase of dementia (MCI) and clinical stages of AD. Other studies are necessary to establish a direct link between BDNF peripheral levels and AD longitudinal course, as well as the role of other factors, such as blood cell activation, in determining these events.

Systemic inflammation might cause neuronal damage and sustain neurodegenerative diseases and behavior impairment, with the participation of pro-inflammatory cytokines, like tumor necrosis factor (TNF)-α and interleukin (IL)-18. However, the potential contribution of these cytokines to behavioral impairment in the long-term period has not been fully investigated.

MicroRNAs (miRNAs) are small non-coding nucleic acids able to post-transcriptionally regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been estimated that at least 1% of the human genome encodes miRNA and every miRNA can regulate up to 200 mRNAs. These findings suggest that dysregulation of miRNA expression could be associated with several human pathological conditions including central neurological disorders. Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. The characteristic symptoms are a progressive loss of memory and other cognitive functions due to the impairment of particular types of neurons and synapses, leading to neuronal death. At present, the available symptomatic treatments can only slow down disease progression without stopping it. miRNAs are widely found within the nervous system where they are key regulators of functions such as neurite outgrowth, dendritic spine morphology, neuronal differentiation, and synaptic plasticity. This has been the clue for considering miRNAs crucial molecules to be studied in AD, and nowadays, dysfunction of miRNAs in AD is increasingly recognized. In this review, we summarized existing evidence about miRNAs as biomarkers or therapeutic agents. The field of miRNAs as biomarkers is more advanced in terms of human data, and it is likely that miRNAs will be used successfully in the near future. Given the huge number of miRNAs potentially involved in diagnostics, miRNA panels will be used for specific tasks such as the stage of the disease, the risk prediction, and disease progression. The field of miRNAs as therapeutics is rapidly developing, and it offers a huge variety of solutions. These include positive effects related to beta-amyloid or tau reduction, increased number of neurons, inhibition of apoptosis, protection of synapses, transformation of other cellular elements into missing/deficient neurons in AD, and so on. It is predictable that both areas of research will be carried forward. However, given the absence of an AD therapy able to stop or reverse the disease, it is desirable to accelerate research on miRNAs as therapeutic agents.

Parkinson’s disease (PD) patients, besides motor dysfunctions, may also display mild cognitive deficits (MCI) which increase with disease progression. The neurotrophin brain-derived neurotrophic factor (BDNF) plays a role in the survival of dopaminergic neurons and in the regulation of synaptic connectivity. Moreover, the brain and peripheral level of this protein may be significantly reduced in PD patients. These data suggest that a cognitive rehabilitation protocol aimed at restoring cognitive deficits in PD patients may also involve changes in this neurotrophin. Thus, in this pilot study we evaluated the effect of a cognitive rehabilitation protocol focused on the training of executive functioning and measured BDNF serum levels in a group of PD patients with mild cognitive impairment, as compared to the effect of a placebo treatment (n=7/8 group). The results showed that PD patients undergoing the cognitive rehabilitation, besides improving their cognitive performance as measured with the Zoo Map test, also displayed increased serum BDNF levels as compared to the placebo group. These findings suggest that BDNF serum levels may represent a biomarker of the effects of cognitive rehabilitation in PD patients affected by MCI. However, the functional significance of this increase in PD as well as other neuropathological conditions remains to be determined.