Aims Microglia undergo profound structural and functional

The gap

Evidence profile

Stated in the future work and cells future research and abstract sections of the source papers, classified as general, spanning 3 journals.

Supporting evidence — 3 representative gaps

• Targeting microglia-mediated neuroinflammation in Alzheimer’s disease: mechanisms and therapeutic approaches (2026) · Frontiers in Immunology · doi

  The paradigm of AD research has undergone a profound transformation, evolving from a strictly neurocentric view focused on amyloid and tau proteinopathies to a more holistic framework that positions the innate immune system as a central driver of pathogenesis. As detailed in this review, microglia are not merely passive responders to neurodegeneration but are dynamic, plastic orchestrators that can determine the trajectory of the disease. The recognition of their “double-edged” nature—shifting from homeostatic guardians to protective barriers (DAM), and ultimately to chronic executioners of neurotoxicity—provides a critical explanation for the failure of earlier broad-spectrum anti-inflammatory trials. It highlights that the success of immunomodulatory therapies hinges not on suppression alone, but on the precise, stage-dependent modulation of microglial phenotypes. Moving forward, the clinical translation of microglia-targeted therapies faces several pivotal challenges that define the future research agenda. First, the timing of intervention is paramount. Given the dichotomous role of microglia, therapeutic strategies must be stratified according to disease stage. Early-stage interventions might focus on enhancing TREM2-mediated chemotaxis and phagocytosis to contain nascent pathology, whereas late-stage therapies should prioritize the blockade of the NLRP3 inflammasome to arrest catastrophic neuroinflammation and synaptic loss.

  generalstated in future workevidence 5/5
  Keywords: stage microglia therapies framework detailed disease critical microglial ammasome paradigm undergone profound transformation evolving strictly
• Roles of Microglia and Astrocytes in Neuroinflammation of Alzheimer's Disease: From Mechanisms to Therapeutics (2026) · Theoretical and Natural Science · doi

  Further studies are needed to understand the roles of microglia and astrocytes in AD-related neuroinflammation. - The development of therapeutics targeting Aβ and tau proteins should be prioritized. - Research on the interaction between microglia and astrocytes may lead to new insights into AD pathogenesis.

  generalstated in cells future researchevidence 5/5
  Keywords: further studies needed understand roles microglia astrocytes ad-related
• Early Regional Microglial Remodelling in the Hippocampus of the <i>App</i> ^{<i>NL‐G‐F</i>} Alzheimer's Model (2026) · Neuropathology and Applied Neurobiology · doi

  ABSTRACT Aims Microglia undergo profound structural and functional changes during Alzheimer's disease, yet the earliest stages of morphological remodelling that occur prior to amyloid deposition remain poorly defined.

  generalstated in abstractevidence 4/5
  Keywords: abstract aims microglia undergo profound structural functional changes alzheimer disease earliest stages morphological remodelling occur

Questions about this gap