Shared Immune and Cellular Mechanisms Linking Alzheimer’s Disease and Motor Neuron Disease: Implications for Aging Trajectories and Healthspan

Neurodegenerative disorders such as Alzheimer’s disease (AD) and motor neuron disease (MND, including amyotrophic lateral sclerosis, ALS) are major contributors to age-related disability and loss of independence. Although they affect distinct neural circuits — AD primarily impairing cognition, MND primarily impairing motor function — both diseases share overlapping cellular hallmarks, including chronic neuroinflammation, disrupted proteostasis, and progressive neuronal loss. Comparing these two conditions offers a valuable opportunity to identify convergent immune and cellular mechanisms that drive neurodegeneration, and to understand how these processes intersect with the broader biology of aging. As global life expectancy rises, understanding these shared mechanisms is essential for promoting healthy longevity.In both AD and MND, the central nervous system is not an isolated environment but a dynamic landscape where neurons, glial cells, and peripheral immune components engage in complex and evolving crosstalk. Microglia and astrocytes, once considered passive support cells, are now recognized as key regulators of neuroinflammation, synaptic remodeling, and tissue repair. Dysregulated immune responses — marked by chronic inflammation and aberrant glial activation — intersect with, but are mechanistically distinct from, other hallmarks of aging that also drive neurodegeneration, including impaired proteostasis (the breakdown of protein quality-control systems responsible for clearing misfolded or toxic protein aggregates) and altered intracellular signaling pathways. Disentangling how immune dysfunction interacts with these related but distinct processes is essential for accurately understanding disease progression and accelerated functional decline.This Research Topic aims to explore the immune mechanisms and cellular interactions that underpin AD and MND, with a focus on how these processes influence aging trajectories and healthspan. We welcome contributions that examine innate and adaptive immune responses, neuroimmune communication, and the role of systemic inflammation in disease pathology. Studies investigating cell–cell interactions, including neuron–glia, glia–glia, and brain–periphery signaling, are particularly encouraged. We also welcome studies using model systems relevant to mechanistic dissection of these pathways, including invertebrate models (e.g., C. elegans, Drosophila), cellular and organoid models of neurodegeneration, and animal models, alongside human clinical and omics-based studies.We are also interested in emerging areas such as single-cell and spatial omics approaches, biomarkers of immune dysfunction, and therapeutic strategies targeting neuroinflammation and immune modulation. Comparative and cross-disease perspectives that identify shared or divergent mechanisms between AD and MND are highly valued, as they may reveal common pathways amenable to intervention.By advancing our understanding of how immune dynamics and cellular networks contribute to neurodegeneration, this Research Topic seeks to identify novel targets for intervention and support the development of strategies that preserve cognitive and motor function into later life. Topic editors: Hazel Quek, Fazeleh Etebar, Jenny N.T. Fung, Jeffrey Liddell, Simon Maksour, Phillip Kenneth West Source: https://www.frontiersin.org/research-topics/79951/shared-immune-and-cellular-mechanisms-linking-alzheimers-disease-and-motor-neuron-disease-implications-for-aging-trajectories-and-healthspan