About this Research Topic
Metabolic deficiencies are prominent in Alzheimer’s disease (AD). Reductions in brain glucose metabolism and cytochrome oxidase enzyme maximum velocity are observed in AD subjects. Changes to metabolism are also observed systemically in blood, skin, and muscle tissue. AD risk is modulated by metabolic disorders including diabetes. The number one risk factor for AD, aging, is hallmarked by reductions in metabolism. GWAS studies are increasingly identifying risk alleles associated with metabolic and mitochondrial pathways. Molecular studies of AD brain show an overall reduction in the number of intact mitochondria and mitochondrial DNA. Mitochondrial function/dysfunction plays a role in protein aggregation, inflammation, and cell death; all events observed in AD. Overall, metabolism and mitochondrial function/dysfunction are strongly associated with AD.
The goal of this Research Topic is to further understand metabolic changes in AD and how metabolism interacts with AD risk factors and pathologies. There are unaddressed questions in the field of brain metabolism and AD which include:
1. The role of genetic risk factors for sporadic AD (such as ApoE) in non-cell autonomous functions
2. The intersection between metabolism and inflammation
3. The role of metabolism in protein aggregation
4. How current therapeutic efforts may target metabolism and downstream inflammation/protein aggregation
5. The role of novel metabolism/mitochondrial genes identified by GWAS in pathological mechanisms
6. The role of metabolism in the communication between neurons and glia in AD.
7. How do we leverage existing model systems to address questions of brain metabolism in the context of AD and can we develop better models?
The field of brain metabolism in AD is emerging and generating large interest from a therapeutic standpoint. Progress in filling these knowledge gaps will advance will open new therapeutic avenues for this devastating disease.
Keywords: Metabolism, Inflammation, Alzheimer’s Disease, ApoE, Bioenergetics
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