Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease

Daulatzai, Mak Adam

doi:10.1002/jnr.23777

Cited by 364 publications

(274 citation statements)

References 452 publications

(515 reference statements)

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“…These risk factors trigger neuroinflammation, oxidative-nitrosative stress; decrease NO, and endothelin increase, Amyloid-β deposition, cerebral amyloid angiopathy, and blood-brain barrier disruption. Inflammation trigger long term damage, involving fatty acids, DNA, mitochondria and results in ATP hypometabolism, amyloid B deposition, endothelial dysfunction and blood-brain barrier disruption [57].…”

Section: Discussionmentioning

confidence: 99%

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Karahmet¹,

Prnjavorac²,

Sejranić³

et al. 2018

J Alzheimers Dis Parkinsonism

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IntroductionAlzheimer's disease characterized clinically by a progressive and gradual decline in cognitive function and neuropathologically, by the presence of neuronal threats, specific neuron loss, synapse loss and disturbance of cholinergic synapses. Most people with Alzheimer's have the late-onset form of the disease, in which the symptoms become apparent in their mid-60s. Genetic Basis of Metabolic Changes in Alzheimer's DiseasesThe apolipoprotein E (APOE) gene is involved in late-onset Alzheimer's. This gene has several forms. One of them, APOE ε4, increases a person's risk of developing AD and is associated with an earlier age onset. Around 0.1% of the cases are familial forms of autosomal dominant inheritance, which has an onset before age 65 [1]. This form of the disease is known as onset familial Alzheimer's disease. Most of the autosomal dominant familial AD can be attributed to mutations in one of three genes: those encoding amyloid precursor protein (APP) and presenilins1 and 2 [2]. Most of the mutations in the APP and presenilin genes increase the production of a small protein called Aβ42, which is the main component of senile plaques [3]. Some of the mutations merely alter the ratio between Aβ42 and the other major forms particularly Aβ40 without increasing Aβ42 levels [4,5]. The major hallmarks of AD pathology are masses of the extracellular β-amyloid peptide (Aβ) and neurofibrillary tangles of the microtubule binding protein tau [6,7]. Aβ has crucial importance in the relation of AD as well as the crucial role of its pathogenesis. The neurotoxic potential of the Aβ peptide results from its biochemical properties, favoring aggregation into insoluble oligomers and protofibrils [7]. Etiological treatment of AD is AbstractAlzheimer disease (AD) is common worldwide and almost every case has comorbidities. One of the most common comorbidities of AD is Diabetes mellitus (DM), with or without metabolic syndrome. Both diseases effect nerve tissue and successful treatment would improve the status of the patient. In patients with Alzheimer disease treatment of DM, the treatment could be harmful to the AD, because of that high insulin intake. This may lead to progression of AD. Insulin is considered the best treatment for DM, but insulin therapy could increase comorbidity with AD. No specific therapy for AD is known up to date, so because of that DM is one of the most important risk for AD, concomitant therapy for DM should be planned very carefully. All options of DM therapy should be considered, and different mechanisms of anti-diabetic drugs are preferable. Treatment of AD is more complex metabolic syndrome is present. Any inflammation causes local tissue damage, including brain tissue during AD. Release of interleukins, primarily TNF-α, IL-6, IL-1β in the presence of adipokine leptin, maintains chronic inflammatory status in local brain tissue. Thus, low doses of immunosuppressant therapy should be considered for treatment of AD in future. To delay apoptosis of nerve tissue cells, brain and nerve tissue...

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Section: Discussionmentioning

confidence: 99%

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Karahmet¹,

Prnjavorac²,

Sejranić³

et al. 2018

J Alzheimers Dis Parkinsonism

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“…This neuronal damage and these dysfunctions may cause glucose hypometabolism in different brain areas. Cerebral hypoperfusion and glucose hypometabolism are pathological mechanisms involved in both grey and white matter atrophy, cognitive decline, and Alzheimer's disease [28]. Abnormalities of brain glucose utilization were also studied in autoimmune vasculitis such as systemic lupus erythematosus.…”

Section: Discussionmentioning

confidence: 99%

Altered Brain Glucose Consumption in Cogan’s Syndrome

Mora

Ruffini

Ghetti

et al. 2016

Journal of Ophthalmology

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Purpose. Prospective, controlled cohort study to investigate possible alterations in brain glucose metabolism (CMRglc) in patients with Cogan's syndrome (CS). Patients and Methods. Functional mapping of the CMRglc was obtained by quantitative molecular imaging positron emission tomography, combined with computed tomography (FDG-PET/CT). The patients were divided into three clinical groups: typical CS; atypical CS (ACS); autoimmune inner ear disease (AIED). The unmatched control group (CG) consisted of subjects requiring FDG-PET/CT for an extracranial pathology. Statistical mapping searched areas of significant glucose hypometabolism in all the affected patients (DG) and in each clinical subgroup. The results were compared with those of the CG. Results. 44 patients were enrolled (DG) and assigned to the three study groups: 8 patients to the CS group; 21 patients to the ACS group; and 15 to the AIED group. Sixteen subjects formed the CG group. Areas of significant brain glucose hypometabolism were identified in all the study groups, with the largest number and extension in the DG and CS. Conclusions. This study revealed areas of significantly altered CMRglc in patients with CS (any subform) without neurologic complains and normal conventional neuroimaging. Our results suggest that FDG-PET/CT may represent a very useful tool for the global assessment of patients with Cogan's syndrome.

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“…There are two hypotheses regarding neurodegeneration in brain aging, connected to low energy fuel supply, glucose hypometabolism and its complications for normal functioning [59], and microglia activation with associated secondary effect. In these hypothetical conditions, there are sexually divergent differences in gene expression in aging brain with comparing the number of gene expression changes in both males and females, and separating gene expression profiles based on up or downregulation.…”

Section: Hypothesis On Brain Aging and Neurodegeneration During Perimmentioning

confidence: 99%

“…The mouse female transgenic model of familial AD revealed that ovariectomy induces a shift in fuel availability and metabolism in the hippocampus, with an increase of enzymes required for long-chain fatty acid and ketone body metabolism, to obtain brain energy [46,60]. Glucose hypometabolism associated to cerebral hypoperfusion initiated with perimenopausal atherosclerosis [61], hypercholesterolemia, nitric oxide, and impairment of redox homeostasis is considered as the key pathophysiologic promoter of neurodegeneration [59], and the known differences in regional brain metabolism make some women prone to AD [62].…”

Section: Hypothesis On Brain Aging and Neurodegeneration During Perimmentioning

confidence: 99%

Neuroprotection in Perimenopausal Women

Russu¹,

Antonescu²

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Endocrine and neural senescence overlap in time, by intertwined complex feedback loops. Womens' brain is genetically more prone to suffer during life, and perimenopause is a "critical period" in neuroaging, when the degenerative processes begin. Many hypotheses on the multifactorial nature of women's brain aging are elaborated, and tested in high-tech research centers. The most analyzed Alzheimer's disease (AD) is characterized not only by Aβ oligomers and fibrils accumulation, but also by metabolic and inflammatory changes, with the onset during menopausal transition and early years of menopause. Deep analysis of endocrine, neural, and metabolic pathways are giving new insights to the sequential view of Aβ-centric in AD pathogenesis, prevention, and treatment from perimenopause, for maintaining women's neurological health.

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Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease

Cited by 364 publications

References 452 publications

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Altered Brain Glucose Consumption in Cogan’s Syndrome

Neuroprotection in Perimenopausal Women

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