Alzheimer’s Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question “Are salivary biomarkers reliable for the diagnosis of Alzheimer’s Disease?” Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease.

Parkinson’s Disease (PD) is a common neurodegenerative disease which manifests with motor features, such as bradykinesia, resting tremor, rigidity, and postural instability. Using the non-invasive technique of saliva collection, we designed a systematic review to answer the question “Are salivary biomarkers reliable for the diagnosis of Parkinson’s Disease?”. Following inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Mostly proteins were reported as potential biomarkers in saliva. Based on meta-analysis, in PD patients, salivary levels of total alpha-synuclein were significantly decreased, and those of oligomeric alpha-synuclein were significantly increased. Also, according to pooled AUC, heme oxygenase-1 demonstrated significant predictive value for saliva-based PD diagnosis. In conclusion, some potential biomarkers, especially alpha-synuclein, can be altered in the saliva of PD patients, which could be reliably useful for early diagnosis of this neurodegenerative disease differentiating other synucleopathies.

Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington’s disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.

Cancer is one of the leading causes of death worldwide. Evidence indicates that extracellular vesicles are involved in cancer development and may be used as promising biomarkers in cancer detection. Concomitantly, saliva constitutes a non-invasive and inexpensive source of biomarkers. This systematic review investigates the use of salivary extracellular vesicles in detecting cancers located outside of the head and neck. PubMed, Web of Science, Scopus, and Embase were thoroughly searched from database inception to 16 July 2024. Data from sixteen eligible studies were analyzed, including glioblastoma, lung, esophageal, gastric, prostate, hepatocellular, breast, and pancreatobiliary tract cancers. The findings highlight strong diagnostic potential for lung and esophageal cancers, where specific exosomal RNAs and proteins demonstrated high accuracy in distinguishing cancer patients from healthy individuals. Additionally, biomarkers in glioblastoma showed prognostic value, while those in hepatocellular and pancreatobiliary cancers exhibited potential for early detection. However, gastric and prostate cancer biomarkers showed limited reliability, and breast cancer biomarkers require further validation. In conclusion, salivary extracellular vesicles present potential in non-invasive detection across multiple cancer types; however, their diagnostic power needs further research, including standardization and large-scale validation.

Oral cancer (OC) constitutes a significant health problem globally. There is an urgent need to develop novel biomarkers for OC diagnosis. This meta-analysis aimed to analyze the potential of salivary lactate dehydrogenase (LDH), matrix metalloproteinase-9 (MMP-9), and chemerin as OC biomarkers. The meta-analysis was conducted according to the PRISMA statement guidelines and registered in PROSPERO (CRD420251045968). PubMed, Embase, Scopus, and Web of Science databases were thoroughly searched up to 18 April 2025. After screening, thirty-three articles were included in the meta-analysis based on the random-effects model. The meta-analysis revealed a significantly elevated LDH level in OC patients compared with controls (SMD = 4.592, 95% CI: 3.580–5.605, p < 0.001) and with oral potentially malignant disorders (OPMD) (SMD = 2.416, 95% CI: 1.474–3.358, p < 0.001). For poorly versus well-differentiated OC, significantly higher LDH levels were observed in poorly differentiated tumors (SMD = 6.158, 95% CI: 0.739–11.576, p = 0.027). For MMP-9, there was a significant increase in OC compared with controls and a borderline-significant difference compared with OPMD (SMD = 1.507, 95% CI: 0.644–2.369, p = 0.001; SMD = 1.626, 95% CI: −0.097–3.350, p = 0.064, respectively). In comparing poorly versus well-differentiated OC, MMP-9 levels were significantly increased in poorly differentiated tumors (SMD = 1.790, 95% CI: 0.643–2.937, p = 0.003). Chemerin levels were significantly elevated in OC versus controls (SMD = 3.905, 95% CI: 3.210–4.600, p < 0.001) and OPMD (SMD = 1.605, 95% CI: 1.139–2.071, p < 0.001). In conclusion, these findings support the potential use of LDH, MMP-9, and chemerin as adjunctive biomarkers in diagnosing and stratifying OC.

Migraine is a complex neurovascular disorder with a multifactorial pathophysiology involving genetic, metabolic, and environmental factors. Increasing evidence indicates that oxidative stress plays a key role in the development of migraine; however, it is unclear whether oxidative imbalance acts primarily as a causal factor or occurs as a consequence of migraine-related processes. Oxidative stress, defined as an imbalance between reactive oxygen species production and antioxidant defense mechanisms, contributes to neuronal hyperexcitability, mitochondrial dysfunction, and neuroinflammation—key mechanisms underlying migraine pathogenesis. Studies have shown elevated markers of oxidative damage and altered antioxidant enzyme activity in migraine patients. Simultaneously, metabolic and inflammatory changes associated with migraine may further exacerbate oxidative imbalance, suggesting a bidirectional relationship. Furthermore, genetic factors such as SOD2, GPX1, and CAT significantly influence susceptibility to oxidative stress and migraine. The CALCA gene, encoding CGRP, links oxidative stress mechanisms with neurogenic inflammation and activation of the trigeminovascular system. This article reviews the current evidence regarding the role of oxidative stress in migraine and discusses its relationship to molecular and genetic mechanisms. Particular attention is given to genes involved in oxidative pathways, mitochondrial function, and inflammatory responses, which may help explain individual susceptibility and variability in clinical presentation.