Upstream Lipid and Metabolic Systems Are Potential Causes of Alzheimer's Disease, Parkinson's Disease and Dementias
Overview
Authors
Affiliations
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.
Metabolic Dysfunction in Parkinson's Disease: Unraveling the Glucose-Lipid Connection.
Sian-Hulsmann J, Riederer P, Michel T Biomedicines. 2025; 12(12.
PMID: 39767747 PMC: 11673947. DOI: 10.3390/biomedicines12122841.
α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice.
Morais L, Boktor J, Mahmoudiandehkordi S, Kaddurah-Daouk R, Mazmanian S NPJ Parkinsons Dis. 2024; 10(1):208.
PMID: 39477976 PMC: 11525669. DOI: 10.1038/s41531-024-00816-w.
Chalitsios C, Ley H, Gao J, Turner M, Thompson A J Neurol. 2024; 271(10):6956-6969.
PMID: 39230722 PMC: 11447100. DOI: 10.1007/s00415-024-12665-x.
α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice.
Morais L, Boktor J, Mahmoudiandehkordi S, Kaddurah-Daouk R, Mazmanian S bioRxiv. 2024; .
PMID: 38915679 PMC: 11195096. DOI: 10.1101/2024.06.07.597975.
Kwon S, Park K, Yoon K Life (Basel). 2023; 13(12).
PMID: 38137948 PMC: 10744624. DOI: 10.3390/life13122346.