Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann–Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors. In this review, we compare these neurodegenerative diseases from a clinical point of view and highlight common pathways and mechanisms of protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies for overlapping immune dysfunctions in these diseases. These approaches include but are not limited to immunisation, complement cascade blockade, microbiome regulation, inhibition of signal transduction, Treg boosting, and stem cell transplantation.

Introduction: Parkinson’s disease (PD) patients have a significantly higher risk of developing dementia in later disease stages, leading to severe impairments in quality of life and self-functioning. Questions remain on how deep brain stimulation (DBS) affects cognition, and whether we can individualize therapy and reduce the risk for adverse cognitive effects. Our aim in this systematic review is to assess the current knowledge in the field and determine if the findings could influence clinical practice.Methods: We have conducted a systematic review according to PRISMA guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.Results: Sixty-seven studies were included in this systematic review according to the selected criteria. This includes 6 meta-analyses, 18 randomized controlled trials, 17 controlled clinical trials, and 26 observational studies with no control arms. The total number of PD patients encompassed in the studies cited in this review is 3677, not including the meta-analyses.Conclusion: Cognitive function in PD patients can deteriorate, in most cases mildly, but still impactful to the quality of life. The strongest evidence is present for deterioration in verbal fluency, while inconclusive evidence is still present for executive function, memory, attention and processing speed. Global cognition does not appear to be significantly impacted by DBS, especially if cognitive screening is performed prior to the procedure, as lower baseline cognitive function is connected to poor outcomes. Further randomized controlled studies are required to increase the level of evidence, especially in the case of globus pallidus internus DBS, pedunculopontine nucleus DBS, and the ventral intermediate nucleus of thalamus DBS, and more long-term studies are required for all respective targets.

Stroke is a leading cause of disability and the second most common cause of death worldwide, with its incidence increasing due to an aging population. Early diagnosis is crucial for timely medical intervention. Biomarkers serve as objective indicators to predict outcomes, monitor treatment responses, and assess prognosis. This review examines the evolving landscape of stroke biomarkers, highlighting their potential clinical applications and the challenges hindering their widespread use. Blood biomarkers are readily accessible and provide insight into the pathophysiological processes underlying stroke. This review focuses on neuronal and glial biomarkers, as well as those associated with inflammation, thrombosis, excitotoxicity, and neuroprotection. Also, it focuses on genetic biomarkers. The timing of biomarker measurement is particularly critical in the early stages of stroke, when rapid decision-making is essential, and it requires systematic investigation. Although numerous molecules have been proposed as stroke biomarkers in recent years, none have yet been integrated into routine clinical practice. Stroke biomarkers hold great promise for enhancing diagnosis, risk stratification, and personalized treatment strategies. However, well-designed studies and rigorous validation are necessary to bridge the gap between research findings and clinical implementation. Integrating biomarkers with existing diagnostic tools could revolutionize stroke management and improve patient outcomes. Continued research into blood biomarkers and their clinical utility remains imperative for advancing stroke care.

Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease, which creates a significant public health burden. There is a challenge for the optimization of therapies since patients not only respond differently to current treatment options but also develop different side effects to the treatment. Genetic variability in the human genome can serve as a biomarker for the metabolism, availability of drugs and stratification of patients for suitable therapies. The goal of this systematic review is to assess the current evidence for the clinical translation of pharmacogenomics in the personalization of treatment for Parkinson’s disease. Methods: We performed a systematic search of Medline database for publications covering the topic of pharmacogenomics and genotype specific mutations in Parkinson’s disease treatment, along with a manual search, and finally included a total of 116 publications in the review. Results: We analyzed 75 studies and 41 reviews published up to December of 2020. Most research is focused on levodopa pharmacogenomic properties and catechol-O-methyltransferase (COMT) enzymatic pathway polymorphisms, which have potential for clinical implementation due to changes in treatment response and side-effects. Likewise, there is some consistent evidence in the heritability of impulse control disorder via Opioid Receptor Kappa 1 (OPRK1), 5-Hydroxytryptamine Receptor 2A (HTR2a) and Dopa decarboxylase (DDC) genotypes, and hyperhomocysteinemia via the Methylenetetrahydrofolate reductase (MTHFR) gene. On the other hand, many available studies vary in design and methodology and lack in sample size, leading to inconsistent findings. Conclusions: This systematic review demonstrated that the evidence for implementation of pharmacogenomics in clinical practice is still lacking and that further research needs to be done to enable a more personalized approach to therapy for each patient.

Introduction: Parkinson’s disease (PD) is neurodegenerative disease with a multifactorial etiopathogenesis with accumulating evidence identifying microbiota as a potential factor in the earliest, prodromal phases of the disease. Previous research has already shown a significant difference between gut microbiota composition in PD patients as opposed to healthy controls, with a growing number of studies correlating gut microbiota changes with the clinical presentation of the disease in later stages, through various motor and non-motor symptoms. Our aim in this systematic review is to compose and assess current knowledge in the field and determine if the findings could influence future clinical practice as well as therapy in PD.Methods: We have conducted a systematic review according to PRISMA guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.Results: 20 studies were included in this systematic review according to the selected inclusion and exclusion criteria. The search yielded 18 case control studies, 1 case study, and 1 prospective case study with no controls. The total number of PD patients encompassed in the studies cited in this review is 1,511.Conclusion: The link between gut microbiota and neurodegeneration is a complex one and it depends on various factors. The relative abundance of various microbiota taxa in the gut has been consistently shown to have a correlation with motor and non-motor symptom severity. The answer could lie in the products of gut microbiota metabolism which have also been linked to PD. Further research is thus warranted in the field, with a focus on the metabolic function of gut microbiota in relation to motor and non-motor symptoms.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.