Emerging Pathophysiological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: An Old Wine in a New Bottle

Patel, Vishvas N.; Chorawala, Mehul R.; Shah, Maitri B.; Shah, Kashvi C.; Dave, Bhavarth P.; Shah, Manal P.; Patel, Tanvi M.

doi:10.3233/adr-220021

Cited by 23 publications

(11 citation statements)

References 49 publications

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“…The pathophysiological mechanisms underlying structural and functional brain damage in individuals with diabetes are multiple and complex. 31 Strokes, which are part of the many cardiovascular complications associated with diabetes, increase the risk of dementia. 32 However, they cannot fully explain the association between AD and diabetes, as this cannot be reduced to strokes or hypoglycaemia, and do not seem to provide the most satisfying answer.…”

Section: Alzheimer's Disease and Type 2 Diabetes: Many Pathophysiolog...mentioning

confidence: 99%

“…As a result, insulin exerts beneficial effects in the brain as it positively regulates inflammation-driven processes, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and apoptosis and promotes mechanisms involved in cell growth and differentiation, and increased synaptic strength, neuronal survival, memory abilities, and learning. 31 , 34 , 35 , 45 Therefore, when it acts correctly, insulin exerts many benefits in the brain, from long-term neuroprotective and neuromodulatory effects to anorectic activities in the hypothalamus. 46 …”

Section: Alzheimer's Disease and Type 2 Diabetes: Many Pathophysiolog...mentioning

confidence: 99%

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Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer’s Disease

Colin¹,

Szczepański²,

Gérard³

et al. 2023

European Endocrinology

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From an epidemiological and pathophysiological point of view, Alzheimer’s disease (AD) and type 2 diabetes (T2DM) should be considered 'sister' diseases. T2DM significantly increases the risk of developing AD, and the mechanisms of neuronal degeneration themselves worsen peripheral glucose metabolism in multiple ways. The pathophysiological links between the two diseases, particularly cerebral insulin resistance, which causes neuronal degeneration, are so close that AD is sometimes referred to as 'type 3 diabetes'. Although the latest news on the therapeutic front for AD is encouraging, no treatment has been shown to halt disease progression permanently. At best, the treatments slow down the progression; at worst, they are inactive, or cause worrying side effects, preventing their use on a larger scale. Therefore, it appears logical that optimizing the metabolic milieu through preventive or curative measures can also slow down the cerebral degeneration that characterizes AD. Among the different classes of hypoglycaemic drugs, glucagon-like peptide 1 receptor agonists, which are widely used in the treatment of T2DM, were shown to slow down, or even prevent, neuronal degeneration. Data from animal, preclinical, clinical phase II, cohort and large cardiovascular outcomes studies are encouraging. Of course, randomized clinical phase III studies, which are on-going, will be essential to verify this hypothesis. Thus, for once, there is hope for slowing down the neurodegenerative processes associated with diabetes, and that hope is the focus of this review.

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Section: Alzheimer's Disease and Type 2 Diabetes: Many Pathophysiolog...mentioning

confidence: 99%

Section: Alzheimer's Disease and Type 2 Diabetes: Many Pathophysiolog...mentioning

confidence: 99%

Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer’s Disease

Colin¹,

Szczepański²,

Gérard³

et al. 2023

European Endocrinology

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“…Risk factors for the development of AD dementia include advanced age; female sex [ 34 , 35 ], presence of the APOE ε4 allele, encoding isoform apolipoprotein 4 (ApoE4); other genetic and epigenetic variations [ 36 , 37 , 38 ]; brain injury [ 39 ]; and environmental factors and stressors [ 40 , 41 ], including a low level of education [ 42 , 43 ] and other lifestyle factors [ 44 ]; infections [ 45 ]; cardiovascular disease [ 46 , 47 ]; type 2 diabetes mellitus [ 48 , 49 ]; and other comorbid metabolic diseases [ 50 ].…”

Section: Risk Factors and Biomarkers Of Alzheimer’s Diseasementioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.

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“…In the pathophysiology of diabetes mellitus, hyperglycemia could lead to a series of pathophysiological changes that impair vascular endothelial function [ 1 , 2 ]. These vascular damages might ultimately lead to atherosclerosis or contribute to other cardiovascular events [ 3 ]. Endothelial dysfunction frequently occurs in type 2 diabetes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine (m6A) writer METTL3 accelerates the apoptosis of vascular endothelial cells in high glucose

Meng

Chen

et al. 2023

Heliyon

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Emerging Pathophysiological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: An Old Wine in a New Bottle

Cited by 23 publications

References 49 publications

Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer’s Disease

Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer’s Disease

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

N6-methyladenosine (m6A) writer METTL3 accelerates the apoptosis of vascular endothelial cells in high glucose

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