Abstract
Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is characterised pathologically by the accumulation of amyloid beta and tau protein aggregates. Currently, there are no approved disease modifying therapies for clearance of either of these proteins from the brain of people with AD. As well as abnormalities in protein aggregation, other pathological changes are seen in this condition. The function of mitochondria in both the nervous system and rest of the body is altered early in this disease, and both amyloid and tau have detrimental effects on mitochondrial function. In this review article, we describe how the function and structure of mitochondria change in AD. This review summarises current imaging techniques that use surrogate markers of mitochondrial function in both research and clinical practice, but also how mitochondrial functions such as ATP production, calcium homeostasis, mitophagy and reactive oxygen species production are affected in AD mitochondria. The evidence reviewed suggests that the measurement of mitochondrial function may be developed into a future biomarker for early AD. Further work with larger cohorts of patients is needed before mitochondrial functional biomarkers are ready for clinical use.
Highlights
Cellular metabolic changes within the brains of people with Alzheimer’s disease (AD)are seen very early in the condition, and often precede the development of both amyloid plaques [1,2,3,4] and neurofibrillary tangles [5,6,7,8]
This suggests that the functional changes seen in the mitochondria of AD fibroblasts may not be a direct consequence of electron transport chain (ETC) activity, but caused by the substrates that interact with the different complexes
This study shows that reduced Complex I activity leads to a redistribution of tau towards the cell stoma, which can potentiate the development of NFT and cell death, suggesting that tau pathology can be exacerbated by poor mitochondrial function
Summary
Cellular metabolic changes within the brains of people with Alzheimer’s disease (AD). Mitochondria are in a constant state of flux, altering morphology and localization depending on energy demands or metabolic stresses within the cell [13]. Mitochondria exist in a dynamic network, altering shape in response to stress or as a result of the metabolic demands of the cell. Mitochondrial fission is less directly linked to managing the ATP demands of the cell, but is used as a way of identifying defective mitochondria that need to be removed and recycled [23]. Biomedicines 2021, 9, x FOR PEER REVIEW properties of mitochondria This figure displays the different elements mitochondrial described in this uniporter (depicted in green) maintain the matrix concentration of calcium. 5 (F0F1-ATP Synthase enzyme) toCalcium generate ATP This process consumesthe mitochondria via oxygen at complex 4 and NADH at complex
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