Insulin resistance and impaired lipid metabolism as a potential link between diabetes and Alzheimer's disease

Kulas, Joshua A.; Weigel, Thaddeus K.; Ferris, Heather A.

doi:10.1002/ddr.21643

Cited by 19 publications

(13 citation statements)

References 164 publications

(194 reference statements)

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“…Of note, disturbed immune response negatively affects organs, including the brain. Furthermore, metabolic dysfunction in T2D, obesity, and insulin resistance plays a role in promoting cognitive dysfunction and impacts the pathogenesis of AD [ 58 ].…”

Section: Insulin Resistance As a Common Factor Linking Obesity T2dm And Admentioning

confidence: 99%

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Litwiniuk

Bik

Kalisz

et al. 2021

IJMS

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Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.

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Section: Insulin Resistance As a Common Factor Linking Obesity T2dm And Admentioning

confidence: 99%

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Litwiniuk

Bik

Kalisz

et al. 2021

IJMS

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“…Cerebral insulin resistance has been accepted as contributing to the neurodegenerative process in AD by activating oxidative stress, cytokine production, and apoptotic process [41]. It is also the link between sporadic AD and its risk factor of diabetes [42]. Furthermore, age-related decline in the ability of glucose to cross the BBB might lead to the production of Aβ plaques and tau-containing neurofibrillary tangles (neuro-energetic hypothesis) [43].…”

Section: Pathophysiological Hypotheses and Associated Biomarkersmentioning

confidence: 99%

Utility of Animal Models to Understand Human Alzheimer’s Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals

Qin

Prins

Groeneveld

et al. 2020

IJMS

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To diagnose and treat early-stage (preclinical) Alzheimer’s disease (AD) patients, we need body-fluid-based biomarkers that reflect the processes that occur in this stage, but current knowledge on associated processes is lacking. As human studies on (possible) onset and early-stage AD would be extremely expensive and time-consuming, we investigate the potential value of animal AD models to help to fill this knowledge gap. We provide a comprehensive overview of processes associated with AD pathogenesis and biomarkers, current knowledge on AD-related biomarkers derived from on human and animal brains and body fluids, comparisons of biomarkers obtained in human AD and frequently used animal AD models, and emerging body-fluid-based biomarkers. In human studies, amyloid beta (Aβ), hyperphosphorylated tau (P-tau), total tau (T-tau), neurogranin, SNAP-25, glial fibrillary acidic protein (GFAP), YKL-40, and especially neurofilament light (NfL) are frequently measured. In animal studies, the emphasis has been mostly on Aβ. Although a direct comparison between human (familial and sporadic) AD and (mostly genetic) animal AD models cannot be made, still, in brain, cerebrospinal fluid (CSF), and blood, a majority of similar trends are observed for human AD stage and animal AD model life stage. This indicates the potential value of animal AD models in understanding of the onset and early stage of AD. Moreover, animal studies can be smartly designed to provide mechanistic information on the interrelationships between the different AD processes in a longitudinal fashion and may also include the combinations of different conditions that may reflect comorbidities in human AD, according to the Mastermind Research approach.

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“…Indeed, recent reports demonstrate a clear relationship between brain function and energy homeostasis. For instance, Alzheimer’s disease (AD) shows metabolic defects, including glucose uptake deficiency in the brain, insulin resistance, and even food intake alterations [ 17 , 18 ]. Furthermore, neurodegeneration is also associated with metabolic impairment and diabetes [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Mens sana in corpore sano: Does the Glycemic Index Have a Role to Play?

Carneiro

Leloup

2020

Nutrients

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Although diet interventions are mostly related to metabolic disorders, nowadays they are used in a wide variety of pathologies. From diabetes and obesity to cardiovascular diseases, to cancer or neurological disorders and stroke, nutritional recommendations are applied to almost all diseases. Among such disorders, metabolic disturbances and brain function and/or diseases have recently been shown to be linked. Indeed, numerous neurological functions are often associated with perturbations of whole-body energy homeostasis. In this regard, specific diets are used in various neurological conditions, such as epilepsy, stroke, or seizure recovery. In addition, Alzheimer’s disease and Autism Spectrum Disorders are also considered to be putatively improved by diet interventions. Glycemic index diets are a novel developed indicator expected to anticipate the changes in blood glucose induced by specific foods and how they can affect various physiological functions. Several results have provided indications of the efficiency of low-glycemic index diets in weight management and insulin sensitivity, but also cognitive function, epilepsy treatment, stroke, and neurodegenerative diseases. Overall, studies involving the glycemic index can provide new insights into the relationship between energy homeostasis regulation and brain function or related disorders. Therefore, in this review, we will summarize the main evidence on glycemic index involvement in brain mechanisms of energy homeostasis regulation.

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Insulin resistance and impaired lipid metabolism as a potential link between diabetes and Alzheimer's disease

Cited by 19 publications

References 164 publications

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Utility of Animal Models to Understand Human Alzheimer’s Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals

Mens sana in corpore sano: Does the Glycemic Index Have a Role to Play?

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