Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias

Brain health requires circuits, cells and molecular pathways to adapt when challenged and to promptly reset once the challenge has resolved. Neurodegeneration occurs when adaptability becomes confined, causing challenges to overwhelm neural circuitry. Studies of rare and common neurodegenerative diseases suggest that the accumulation of lipids can compromise circuit adaptability. Using microglia as an example, we review data that suggest increased lipid concentrations cause dysfunctional inflammatory responses to immune challenges, leading to Alzheimer's disease, Parkinson's disease and dementia. We highlight current approaches to treat lipid metabolic and clearance pathways and identify knowledge gaps towards restoring adaptive homeostasis in individuals who are at-risk of losing cognition.

Automated summary

Brain health relies on adaptability and resetting after challenges. Neurodegeneration occurs when adaptability is restricted. Accumulation of lipids compromises adaptability in neural circuits. Treatment targeting lipid metabolism can restore adaptive homeostasis in individuals at risk of cognitive decline.