The complexity of neurodegenerative disorders necessitates an integrative approach that incorporates morphological, functional, and molecular biomarkers. The advent of highly sensitive single-molecule array (Simoa®) assays has significantly enhanced the accuracy of blood-based biomarker quantification, including glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p-tau181). This study evaluates the diagnostic utility of these biomarkers in neurodegenerative diseases. We analyzed data from 279 individuals from the PADUA-CESNE cohort: 120 with Parkinson's disease (PD), 88 with Alzheimer's disease (AD), 16 with frontotemporal dementia (FTD), 11 with multiple system atrophy (MSA), 14 with progressive supranuclear palsy (PSP), and 30 cognitively unimpaired controls. NfL levels were significantly lower in PD and AD compared to atypical parkinsonisms and FTD, effectively distinguishing MSA and PSP from controls. NfL also negatively correlated with Montreal Cognitive Assessment (MoCA) scores in AD and PD, indicating its association with cognitive decline. Elevated GFAP levels were observed in both PD and AD and inversely correlated with global cognition. Combining GFAP and p-tau181 improved AD differentiation from PD and other parkinsonian disorders, while the integration of all three biomarkers facilitated the distinction between AD and FTD. Notably, lower NfL levels (<20 ng/L) in conjunction with elevated p-tau181 were indicative of AD, whereas NfL levels below 40 ng/L were suggestive of PD. In conclusion, NfL serves as a sensitive indicator of neurodegeneration, albeit with limited specificity. However, by establishing biomarker concentration thresholds and integrating complementary biomarkers, blood-based assays may enhance the differential diagnosis of neurodegenerative diseases, providing valuable clinical insights.

Researchers are increasingly focusing on understanding the microbiota’s influence on disease susceptibility and overall health. The vast number of microorganisms in our gastrointestinal tract and their extensive surface area underscore their undeniable impact on well-being. Viewing the gut microbiome as a distinct pool of microbial genetic information that interacts with the human genome highlights its pivotal role in genetically predisposed diseases. Investigating this complex crosstalk may lead to the development of novel therapeutic strategies—such as targeting dysbiosis—to complement conventional treatments and improve patient care. Parkinson’s disease (PD) is a multifactorial condition originating from a combination of genetic and environmental risk factors. Compelling evidence points to the enteric nervous system as an initial site of pathological processes that later extend to the brain—a pattern known as the ‘body-first’ model. Furthermore, most patients with PD exhibit both qualitative and quantitative alterations in the composition of the gut microbiota, including dysbiosis and small intestinal overgrowth. Nonetheless, the existing literature predominantly addresses fecal microbiota, while knowledge of upper intestinal sections, like the duodenum, remains scarce. Given the potential for microbiota modulation to impact both motor and gastrointestinal symptoms, further research exploring the therapeutic roles of balanced diets, probiotics, and fecal transplants in PD is warranted.

Researchers are increasingly focused on understanding how the microbiota influences disease susceptibility and contributes to overall health. Given the vast number of microorganisms inhabiting our gastrointestinal tract and the extensive surface area they occupy, their impact on our well-being is undeniable. For example, when we consider the gut microbiota's collective genetic information—referred to as the microbiome—and view our genetic profile as a blend of both microbial and human genes, it becomes evident that the microbiota may play a pivotal role in the development of genetically predisposed diseases. Investigating these complex interactions could pave the way for new therapeutic strategies, such as targeting dysbiosis, to complement conventional treatments and enhance patient care. Parkinson's disease (PD) is a multifactorial condition characterized by various genetic and environmental factors that collectively increase the risk of developing the disease. There is strong evidence of the involvement of the enteric nervous system where the pathological processes may start initially and to proceed later to the brain. Moreover, it has been observed that most of PD patients exhibit qualitative and quantitative alterations in the composition of the intestinal microbiota, such as dysbiosis and increased proliferation in the small intestine. Despite this evidence, the available literature largely focuses on information regarding the fecal microbiota, while knowledge of the microbiota in the upper sections of the intestine, such as the duodenum, remains limited. Since modulation of the microbiota may have an effect on both motor and gastrointestinal symptoms, further research exploring how a balanced diet, probiotics, and/or fecal transplants may have a role in PD therapy is warranted.