The identification of neuroinflammation as a critical factor in Alzheimer’s disease (AD) has expanded the focus of research beyond amyloid-β and tau pathology. The neuroinflammatory fluid biomarkers GFAP, sTREM2, and YKL-40 have gained attention for their potential in early detection and monitoring of disease progression. Plasma GFAP has demonstrated promise in predicting the conversion from mild cognitive impairment to AD dementia, while sTREM2 highlights microglial activation, although there are conflicting results regarding its dynamics in AD pathogenesis. Advanced imaging techniques, such as PET tracers targeting TSPO and MAO-B, have also been developed to visualize glial activation in vivo, offering spatial and temporal insights into neuroinflammatory processes. However, the clinical implementation of these biomarkers faces challenges due to their lack of specificity, as many of them can be elevated in other conditions. Therapeutic strategies targeting neuroinflammation are emerging, with TREM2-targeting therapies and antidiabetic drugs like GLP-1 receptor agonists showing potential in modulating microglial activity. Nevertheless, the complexity of neuroinflammation, which encompasses both protective and harmful responses, necessitates further research to fully unravel its role and optimize therapeutic approaches for AD.

Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1β, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (−308 A/G) and a lack of efficacy after NSAID administration (p < 0.01, OR 2.51, 95% CI: 1.33 < OR < 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack.

Background: Stroke-induced immunosuppression (SII) represents a negative rehabilitative prognostic factor associated with poor motor performance at discharge from a neurorehabilitation unit (NRB). This study aims to evaluate the association between SII and gait impairment at NRB admission. Methods: Forty-six stroke patients (65.4 ± 15.8 years, 28 males) and 42 healthy subjects (HS), matched for age, sex, and gait speed, underwent gait analysis using an inertial measurement unit at the lumbar level. Stroke patients were divided into two groups: (i) the SII group was defined using a neutrophil-to-lymphocyte ratio ≥ 5, and (ii) the immunocompetent (IC) group. Harmonic ratio (HR) and short-term largest Lyapunov’s exponent (sLLE) were calculated as measures of gait symmetry and stability, respectively. Results: Out of 46 patients, 14 (30.4%) had SII. HR was higher in HS when compared to SII and IC groups (p < 0.01). HR values were lower in SII when compared to IC subjects (p < 0.01). sLLE was lower in HS when compared to SII and IC groups in the vertical and medio-lateral planes (p ≤ 0.01 for all comparisons). sLLE in the medio-lateral plane was higher in SII when compared to IC subjects (p = 0.04). Conclusions: SII individuals are characterized by a pronounced asymmetric gait and a more impaired dynamic gait stability. Our findings underline the importance of devising tailored rehabilitation programs in patients with SII. Further studies are needed to assess the long-term outcomes and the role of other clinical features on gait pattern.

Background: Frailty is a multidimensional syndrome reflecting reduced physiological reserve, increasingly recognized as a relevant factor in the clinical assessment of older adults with cognitive disorders. Objective: To explore the association between frailty, as measured by the Multidimensional Prognostic Index (MPI), cognitive performance, and plasma biomarkers of Alzheimer’s disease (AD), and to examine the correlation between plasma and cerebrospinal fluid (CSF) biomarkers. Methods: This cross-sectional observational study included 40 patients (mean age 68.0 ± 9.0 years; 42.5% female) undergoing a diagnostic workup for cognitive decline. Patients were classified into AD (n = 20) and non-AD (n = 20) groups based on CSF AT[N] profiles. Frailty was assessed using the MPI. Linear and logistic regression models adjusted for age, sex, and education examined associations between MPI, cognitive scores, and plasma biomarkers (Aβ42, Aβ42/40, p-tau181, NfL). Correlations between plasma and CSF biomarkers and ROC analyses were also performed. Results: The AD group showed significantly higher plasma p-tau181 levels and MPI scores. MPI was positively associated with plasma p-tau181 levels (β = 4.26, p = 0.009). Plasma p-tau181 correlated strongly with CSF p-tau181 (R = 0.523, p < 0.001) and with CSF Aβ42/40 ratio (R = −0.541, p < 0.001) and showed high diagnostic accuracy (AUC = 0.910). Combining MPI with plasma biomarkers improved classification between AD and non-AD cases (AUC = 0.941). Conclusions: These findings support the value of incorporating frailty assessment in the diagnostic process of AD. The integration of geriatric tools and blood-based biomarkers may improve early detection and promote a more comprehensive approach in dementia evaluation.

INTRODUCTION: Plasma phosphorylated tau at threonine 217 (p‐tau217) has shown excellent diagnostic performance for Alzheimer's disease (AD), yet real‐world validation and implementation pathways remain limited. This study assessed its clinical applicability and proposed a practical workflow for memory clinics. METHODS: Plasma p‐tau217, p‐tau181, and neurofilament light chain (NfL) were quantified in consecutive patients referred for cognitive assessment. Cerebrospinal fluid (CSF) amyloid beta (Aβ) 42/40 defined amyloid (A) status, and final etiological diagnoses were reached through multidisciplinary consensus integrating clinical, neuropsychological, and metabolic imaging data. RESULTS: Among 163 patients (mean age 69.3 ± 7.4 years, 52% female), plasma p‐tau217 distinguished A+ from A− individuals (area under the curve [AUC] 0.90, 81% sensitivity, 91% specificity). AD patients showed the highest p‐tau217 levels, while non‐AD neurodegenerative disorders exhibited elevated NfL ( p < 0.001). A dual cut‐off strategy with 95% sensitivity and specificity could have avoided 65% of lumbar punctures. DISCUSSION: Plasma p‐tau217 demonstrated robust clinical validity and supports structured integration into routine diagnostic pathways.

This study evaluated the diagnostic performance of plasma biomarkers for Alzheimer's disease (AD) using an automated platform. In a cohort of 74 consecutive patients, plasma p-Tau181 levels were significantly higher in AD compared to non-AD groups and showed correlation with cerebrospinal fluid biomarkers. Plasma p-Tau181 demonstrated high diagnostic accuracy for AD, with an area under the curve of 0.854. The findings suggest that plasma biomarkers, particularly p-Tau181, could improve the accessibility and efficiency of AD diagnostics in clinical settings, offering a less invasive and cost-effective alternative to traditional methods.