Accelerated Ageing or Selective Neuronal Loss as an Important Cause of Dementia?

Spillane, J. A.; Curzon, G.; Meier‐Ruge, W.; White, Pamela; Goodhardt, Michèle; Iwangoff, P.; Davison, Alan; Bowen, David M.

doi:10.1016/s0140-6736(79)90454-9

Cited by 112 publications

(7 citation statements)

References 17 publications

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“…Studies of PFK showed that inhibition of fructose-2,6-biphosphatase (PFKFB3) led to Aβ accumulation in astrocytes and a higher risk of Aβ toxicity in cultures of human fetal astrocytes. In a study involving autopsy of AD patients, PFK activity was shown to decrease significantly to approximately 10% of the activity in the control group ( Bowen et al, 1979 ). In another study, PFK activity in the frontal and temporal cortex of post-autopsy AD brains was found to be elevated when compared to age-matched non-AD individuals ( Bigl et al, 1999 ).…”

Section: Glycolysis In Admentioning

confidence: 99%

Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease

2021

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Alzheimer’s disease (AD) is the most common form of age-related dementia. Despite decades of research, the etiology and pathogenesis of AD are not well understood. Brain glucose hypometabolism has long been recognized as a prominent anomaly that occurs in the preclinical stage of AD. Recent studies suggest that glycolytic metabolism, the cytoplasmic pathway of the breakdown of glucose, may play a critical role in the development of AD. Glycolysis is essential for a variety of neural activities in the brain, including energy production, synaptic transmission, and redox homeostasis. Decreased glycolytic flux has been shown to correlate with the severity of amyloid and tau pathology in both preclinical and clinical AD patients. Moreover, increased glucose accumulation found in the brains of AD patients supports the hypothesis that glycolytic deficit may be a contributor to the development of this phenotype. Brain hyperglycemia also provides a plausible explanation for the well-documented link between AD and diabetes. Humans possess three primary variants of the apolipoprotein E (ApoE) gene – ApoE∗ϵ2, ApoE∗ϵ3, and ApoE∗ϵ4 – that confer differential susceptibility to AD. Recent findings indicate that neuronal glycolysis is significantly affected by human ApoE isoforms and glycolytic robustness may serve as a major mechanism that renders an ApoE2-bearing brain more resistant against the neurodegenerative risks for AD. In addition to AD, glycolytic dysfunction has been observed in other neurodegenerative diseases, including Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, strengthening the concept of glycolytic dysfunction as a common pathway leading to neurodegeneration. Taken together, these advances highlight a promising translational opportunity that involves targeting glycolysis to bolster brain metabolic resilience and by such to alter the course of brain aging or disease development to prevent or reduce the risks for not only AD but also other neurodegenerative diseases.

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Section: Glycolysis In Admentioning

confidence: 99%

Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease

2021

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“…In patients dying of nonneurological causes, the activity of choline acetyltransferase (CAT), an enzyme that catalyzes the synthesis of acetylcholine, decreases with age for patients between 20 and 50 (McGeer & McGeer, 1976). After age 60 there is no significant correlation between age and CAT activity, but there is a negative correlation between CAT activity and the degree of neurohistological change characteristic of Alzheimer's disease; specifically, the number of senile plaques and the number of neurofibrillary tangles are inversely related to CAT activity (Bowen et al, 1976;Bowen, Spillane, Curzon, Meier-Ruge, White, Goodhardt, Iwangoff, & Davison, 1979). When they are compared with nondemented, age-matched controls, Alzheimer's patients are found to have significantly lower CAT activity (Bowen et al, 1979;Perry, Tomlinson, Blessed, Bergman, Gibson, & Perry, 1978).…”

Section: Psychopharmacological Studies Cholinergic Deficit In Dementiamentioning

confidence: 99%

“…After age 60 there is no significant correlation between age and CAT activity, but there is a negative correlation between CAT activity and the degree of neurohistological change characteristic of Alzheimer's disease; specifically, the number of senile plaques and the number of neurofibrillary tangles are inversely related to CAT activity (Bowen et al, 1976;Bowen, Spillane, Curzon, Meier-Ruge, White, Goodhardt, Iwangoff, & Davison, 1979). When they are compared with nondemented, age-matched controls, Alzheimer's patients are found to have significantly lower CAT activity (Bowen et al, 1979;Perry, Tomlinson, Blessed, Bergman, Gibson, & Perry, 1978). In addition memory loss measured by psychometric testing prior to death is correlated with loss of CAT activity in pa- tients with histologically verified Alzheimer's disease but not in nondemented, age-matched controls (Perry et al, 1978).…”

Section: Psychopharmacological Studies Cholinergic Deficit In Dementiamentioning

confidence: 99%

“…In addition memory loss measured by psychometric testing prior to death is correlated with loss of CAT activity in pa- tients with histologically verified Alzheimer's disease but not in nondemented, age-matched controls (Perry et al, 1978). Analyses of enzymes associated with the neurotransmitters dopamine, GABA, norepinephrine, and serotonin indicate (a) that activities of these enzymes decline with age but to a lesser degree than does CAT activity, and (b) that their activity is not further reduced by senile changes of the Alzheimer's type (Bowen et al, 1976(Bowen et al, , 1979Davies & Maloney, 1976;Perry et al, 1978). These neurochemical studies suggest quite strongly that a loss of central cholinergic activity is the primary neurochemical'abnormality in patients with Alzheimer's disease.…”

Section: Psychopharmacological Studies Cholinergic Deficit In Dementiamentioning

confidence: 99%

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Cholinergic drug effects on memory and cognition in humans.

Mohs¹,

Davis²,

Darley³

1980

Aging in the 1980s: Psychological Issues.

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This chapter summarizes recent attempts to improve normal memory functioning and to alleviate age-related memory deficits by administering drugs that affect transmission at cholinergic synapses. In young adults, a low dose of physostigmine, a short-acting cholinesterase inhibitor, enhanced storage of in formation in long-term memory. Higher doses of physostigmine impaired all aspects of memory. Choline chloride, a precursor to acetylcholine, did not have a substantial effect on memory in a series of four studies with young and elderly adults. It has been difficult to conduct studies of elderly patients suffering from memory loss because of wide individual variations in baseline cognitive abilities and in dose-response curves for cholinergic drugs. A preliminary study utilizing methods that allow for such individual differences indicates that physostigmine can also improve memory in these patients.

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“…The disease affects the brain monoaminergic system, worsening deficits. Extensive evidence reveals neuronal loss and reduced levels of neurotransmitters, receptors and metabolites in the DAergic, noradrenergic (NAergic) and serotonergic (Seroergic) systems in AD patients [20][21][22][23][24][25][26][27][28][29][30][31][32]. This dysfunction is primarily linked to neuropsychiatric symptoms in AD, including depression, agitation, anxiety, apathy, psychosis and disturbances in sleep or appetite in later stages [33,34].…”

Section: Introductionmentioning

confidence: 99%

Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia

Lazarova,

Tsvetanova,

Georgieva

et al. 2024

IJMS

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Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.

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Accelerated Ageing or Selective Neuronal Loss as an Important Cause of Dementia?

Cited by 112 publications

References 17 publications

Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease

Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease

Cholinergic drug effects on memory and cognition in humans.

Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia

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