From synapses to symptoms: understanding cognitive and behavioral changes in neurodegenerative diseases

Neurodegenerative diseases (NDs) are among the most urgent global health challenges, affecting millions worldwide and placing a growing burden on healthcare systems and society. They encompass a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to disruption of neural networks essential for normal cognitive, motor, and sensory function. NDs manifest with symptoms that vary in severity and progression, commonly resulting in declines in memory, cognition, mood, behavior, sleep, mobility, balance, and sensory functions. Despite their prevalence and impact, NDs remain incurable due to complex, multifactorial etiologies and incompletely understood pathogenic mechanisms. Alzheimer’s disease (AD) is the most prevalent ND and the leading cause of dementia. Other major NDs include Huntington’s disease, amyotrophic lateral sclerosis (ALS), prion diseases, and various forms of dementia. While these disorders differ in clinical presentation, they share overlapping pathogenic influences. In addition to genetic determinants, epigenetic and environmental factors contribute to disease development, while aging, sex, stress, lifestyle, immune and endocrine status, and chronic conditions (e.g., hypertension, diabetes) further modulate risk. Common pathogenic mechanisms underlying NDs involve oxidative stress, metabolic dysfunction, neuroimmune alterations, abnormal protein aggregation (e.g., amyloid-β and tau in AD), and neurovascular alterations. Disruption of neuronal connectivity leads to progressive degradation of synapses and axons, ultimately resulting in neuronal death. Understanding these shared pathways is critical for developing therapies with broad potential across multiple NDs.Advances in neuroimaging and fluid biomarkers have improved early and accurate diagnosis. The 2024 update of Alzheimer’s disease diagnostic and staging criteria reflects these developments. Blood-based biomarkers, particularly phosphorylated tau217 (p-tau217), show promise, while neuroimaging methods, including tau PET, are being refined for improved sensitivity and clinical utility. Emerging therapies, such as monoclonal antibodies, are not yet curative, but continued development could significantly improve patient outcomes and global healthcare.This Research Topic focuses on studies investigating the pathogenesis of cognitive impairment in NDs and adopts a multidisciplinary approach, integrating basic and translational neuroscience, neuroimmunology, and neuropsychology, with potential clinical implications. We encourage submissions that present novel findings across all stages of research, from molecular and preclinical studies to human and translational work with direct clinical relevance. Studies exploring diagnostic and prognostic biomarkers, particularly in relation to cognitive or behavioral changes, are highly encouraged. While emphasis is placed on well-established pathogenic factors, such as oxidative stress, energy metabolism, neuroimmune alterations, and neurovascular dysfunction studies addressing other mechanisms of clinical or therapeutic relevance are also welcome.We encourage submission of original research articles, reviews, methods, clinical reports, and other article types on topics including, but not limited to:• Identifying common biomarkers of NDs relevant to cognitive function.• Evaluating biomarkers with diagnostic or prognostic utility for cognitive or behavioral changes.• Developing experimental models, in vitro or in vivo, to study mechanisms of cognitive decline.• Applying translational methodologies, including neuroimaging, electrophysiology (EEG, MEG, fMRI), and digital biomarkers.• Assessing tools and tests for detecting subtle cognitive impairments (memory, language, attention, executive function).• Investigating personalized treatments via gene/cell therapies (CRISPR, stem cells), novel drug delivery systems (nanoparticles, exosomes), or interventions targeting shared mechanisms (protein aggregation, neuroinflammation), using advanced diagnostics (biomarkers, imaging, AI).• Designing strategies for prevention, cognitive preservation, and rehabilitation in neurodegeneration.This Research Topic aims to foster multidisciplinary collaboration and advance understanding of cognitive decline in NDs, ultimately informing diagnostics, therapeutics, and clinical management. Topic editors: Vesna Lukinovic Škudar, Anita Senthinathan, Andrea Zammit Source: https://www.frontiersin.org/research-topics/77011/from-synapses-to-symptoms-understanding-cognitive-and-behavioral-changes-in-neurodegenerative-diseases