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Primary cilia in the mature brain: emerging roles in Alzheimer’s disease pathogenesis

Summary

Primary cilia are small hair-like structures on brain cells that act like sensory antennas, helping regulate memory and thinking ability. In Alzheimer’s disease, these structures become abnormally shaped and function poorly, contributing to memory loss and cognitive decline. The shape and function of primary cilia change as the brain ages and when amyloid plaques develop, suggesting they could be targeted with new treatments to slow Alzheimer’s progression.

Background

Primary cilia are microtubule-based sensory organelles present on most mammalian cells. Dysfunction of primary cilia has been linked to various age-related conditions. Alzheimer’s disease affects more than 38.5 million individuals worldwide, with aging as its most significant risk factor.

Objective

This review synthesizes current findings on the role of primary cilia in the mature brain and mechanisms by which alterations in primary cilia may influence Alzheimer’s disease progression. The authors examine the relationship between primary ciliary dysfunction and key AD pathologies including amyloid-beta plaques and tau tangles.

Results

Primary cilia exhibit dynamic morphological variations across cell types, brain regions, and with age. In AD models, neuronal cilia undergo region-specific alterations including elongation that halts after amyloid accumulation, and expression changes in ciliary GPCRs. Disruption of ciliary proteins impairs Aβ clearance, alters neuroinflammatory responses, and causes cognitive deficits.

Conclusion

Primary cilia function as integrative hubs coordinating intracellular signaling and extracellular interactions relevant to AD pathogenesis. Further mechanistic studies are needed to clarify whether ciliary remodeling represents a causal driver or compensatory response, and to evaluate therapeutic potential of cilia-targeted interventions in human-relevant models.
  • Published in:Frontiers in Cell and Developmental Biology,
  • Study Type:Review,
  • Source: PMID: 41070350, DOI: 10.3389/fcell.2025.1650884
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