Mitochondrial function in Alzheimer's disease

Cooper, JM; Wischik, C. M.; Schapira, Anthony H.V.

doi:10.1016/0140-6736(93)91269-r

Cited by 20 publications

(10 citation statements)

References 7 publications

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“…COX deficiency has been reported in the AD brain in most [40][41][42][43][44] but not all 45,46 studies. In most studies, the deficiency of COX is limited to regions of the brain which also show histopathological damage.…”

Section: Abnormalities In Energy/oxidative Metabolism In Autopsied Admentioning

confidence: 99%

Inherent Abnormalities in Energy Metabolism in Alzheimer Disease: Interaction with Cerebrovascular Compromise

Blass

Sheu

Gibson

2000

Annals of the New York Academy of Sciences

170

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Alzheimer disease (AD) is a form of the dementia syndrome. AD appears to have a variety of fundamental etiologies that lead to the neuropathological manifestations which define the disease. Patients who are at high risk to develop AD typically show impairments of cerebral metabolic rate in vivo even before they show any evidence of the clinical disease on neuropsychological, electrophysiological, and neuroimaging examinations. Therefore, impairment in energy metabolism in AD can not be attributed to loss of brain substance or to electrophysiological abnormalities. Among the characteristic abnormalities in the AD brain are deficiencies in several enzyme complexes which participate in the mitochondrial oxidation of substrates to yield energy. There include the pyruvate dehydrogenase complex (PDHC), the alpha-ketoglutarate dehydrogenase complex (KGDHC), and Complex IV of the electron transport chain (COX). The deficiency of KGDHC may be due to a mixture of causes including damage by free radicals and perhaps to genetic variation in the DLST gene encoding the core protein of this complex. Inherent impairment of glucose oxidation by the AD brain may reasonably be expected to interact synergistically with an impaired supply of oxygen and glucose to the AD brain, in causing brain damage. These considerations lead to the hypothesis that cerebrovascular compromise and inherent abnormalities in the brain's ability to oxidize substrates can interact to favor the development of AD, in individuals who are genetically predisposed to develop neuritic plaques.

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Section: Abnormalities In Energy/oxidative Metabolism In Autopsied Admentioning

confidence: 99%

Inherent Abnormalities in Energy Metabolism in Alzheimer Disease: Interaction with Cerebrovascular Compromise

Blass

Sheu

Gibson

2000

Annals of the New York Academy of Sciences

170

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“…And, reported reductions in CIV activity (87) and CI and CIV deficiencies in AD platelets and brain tissue (88)(89)(90) led to the idea that CIV deficiency could be behind AD pathogenesis (91,92). However, detractors pointed out not only that the reported CIV reductions in AD are below the threshold for dysfunction (93,94), but that similarly small reductions in CIV subunits were observed in other neurodegenerative diseases (95), implying that the CIV deficiencies likely reflected non-AD-specific changes. Moreover, as in PD, additional studies challenged the aforementioned findings, by showing that mitochondrial respiration capacity was unaffected in AD brain and arguing that metabolic alterations in AD are unlikely to be driven by primary OxPhos deficiencies (96).…”

Section: Common Neurodegenerative Disorders and The Mitochondrial Hypmentioning

confidence: 99%

Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas

Area‐Gómez¹,

Guardia‐Laguarta²,

Schon

et al. 2019

Journal of Clinical Investigation

127

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“…Others, however, were unable to replicate such findings [6,38]. There is controversy over which enzyme in the OXPHOS pathway is most affected [6,39]. Discrepancies in the results have not been explained and it is yet to be determined whether nuclear or mitochondrial genes underlie such reported defects [40].…”

Section: Mitochondrial Function In Admentioning

confidence: 84%

“…A number of studies have suggested that a decline in cytochrome c oxidase activity in the brain may be contributing to the expression of AD [32][33][34][35][36][37]. Others, however, were unable to replicate such findings [6,38]. There is controversy over which enzyme in the OXPHOS pathway is most affected [6,39].…”

Section: Mitochondrial Function In Admentioning

confidence: 88%

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Mitochondrial Function and Alzheimer’s Disease

Ojaimi¹,

Byrne²

2001

Neurosignals

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The brain is highly dependent on aerobic metabolism. Normal mitochondrial function is therefore likely to play a critical role in neuronal function and integrity. Defects in the mitochondrial oxidative phosphorylation pathway (OXPHOS) have been demonstrated in aging human tissue including brain. It is not clear whether underlying mitochondrial DNA mutations are responsible for the observed functional defects. The previously reported OXPHOS defects, in particular reduced cytochrome c oxidase activity, in Alzheimer’s disease (AD) are not likely to be due to specific enzyme dysfunction. The falloff in cytochrome c oxidase activity in AD brains is more likely to be related to a global decline in mitochondrial activity manifested by downregulation in mitochondrial number. It is not definitely established where the observed mitochondrial changes are placed in the AD cascade. A number of factors might contribute to the observed changes in OXPHOS function including mitochondrial transport through axonal and dendritic processes, compromised regulatory feedback mechanisms responsible for individual complex-subunit synthesis, and complex assembly.

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Mitochondrial function in Alzheimer's disease

Cited by 20 publications

References 7 publications

Inherent Abnormalities in Energy Metabolism in Alzheimer Disease: Interaction with Cerebrovascular Compromise

Inherent Abnormalities in Energy Metabolism in Alzheimer Disease: Interaction with Cerebrovascular Compromise

Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas

Mitochondrial Function and Alzheimer’s Disease

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