Alzheimer's disease alters oligodendrocytic glycolytic and ketolytic gene expression
| Autor: | Justin B. Miller, Oscar Harari, Carlos Cruchaga, John S. K. Kauwe, Benjamin T. Bikman, Kathie A. Mihindukulasuriya, Erin R. Saito |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Cell type Epidemiology microglia oligodendrocytes Gene Expression Disease Carbohydrate metabolism Biology Biochemistry Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine metabolic RNA-seq profiles Developmental Neuroscience Alzheimer Disease Gene expression Genetics medicine Humans Glycolysis Molecular Biology ketolysis Neurons Microglia Health Policy astrocytes Brain Metabolism glycolysis Ketones Oligodendroglia Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Alternative complement pathway Female Autopsy Neurology (clinical) Geriatrics and Gerontology Alzheimer’s disease Neuroscience 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Alzheimer's & dementia : the journal of the Alzheimer's Association |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1002/alz.12310 |
| Popis: | Introduction Sporadic Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism, which may affect AD onset and progression. Ketolysis has been suggested as an alternative pathway to fuel the brain. Methods RNA-seq profiles of post mortem AD brains were used to determine whether dysfunctional AD brain metabolism can be determined by impairments in glycolytic and ketolytic gene expression. Data were obtained from the Knight Alzheimer's Disease Research Center (62 cases; 13 controls), Mount Sinai Brain Bank (110 cases; 44 controls), and the Mayo Clinic Brain Bank (80 cases; 76 controls), and were normalized to cell type: astrocytes, microglia, neurons, oligodendrocytes. Results In oligodendrocytes, both glycolytic and ketolytic pathways were significantly impaired in AD brains. Ketolytic gene expression was not significantly altered in neurons, astrocytes, and microglia. Discussion Oligodendrocytes may contribute to brain hypometabolism observed in AD. These results are suggestive of a potential link between hypometabolism and dysmyelination in disease physiology. Additionally, ketones may be therapeutic in AD due to their ability to fuel neurons despite impaired glycolytic metabolism. |
| Databáze: | OpenAIRE |
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