Metabolic syndrome and its components in relation to in vivo brain amyloid and neurodegeneration in late middle age

Palta, Priya; Rippon, Brady; Tahmi, Mouna; Sherwood, Greysi; Soto, Luisa M. Solis; Ceballos, Fernando; Laing, Krystal K; He, Hengda; Reitz, Christiane; Razlighi, Qolamreza R.; Teresi, Jeanne A.; Moreno, Herman; Brickman, Adam M.; Luchsinger, José A.

doi:10.1016/j.neurobiolaging.2020.09.023

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…The molecular mechanisms underlying the effect of adipose tissue hypertrophy on neurodegeneration processes are related to APP production in adipose tissue in the metabolic syndrome increases, as well as levels of Aβ and cholesterol in the blood serum. It can eventually lead to increased Aβ transport in the brain and impaired functioning of neurons [ 122 , 123 ].…”

Section: Alzheimer’s Disease and Chronic Inflammatory Diseasesmentioning

confidence: 99%

Alzheimer’s Disease and Inflammaging

et al. 2022

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Alzheimer’s disease is one of the most common age-related neurodegenerative disorders. The main theory of Alzheimer’s disease progress is the amyloid-β cascade hypothesis. However, the initial mechanisms of insoluble forms of amyloid-β formation and hyperphosphorylated tau protein in neurons remain unclear. One of the factors, which might play a key role in senile plaques and tau fibrils generation due to Alzheimer’s disease, is inflammaging, i.e., systemic chronic low-grade age-related inflammation. The activation of the proinflammatory cell phenotype is observed during aging, which might be one of the pivotal mechanisms for the development of chronic inflammatory diseases, e.g., atherosclerosis, metabolic syndrome, type 2 diabetes mellitus, and Alzheimer’s disease. This review discusses the role of the inflammatory processes in developing neurodegeneration, activated during physiological aging and due to various diseases such as atherosclerosis, obesity, type 2 diabetes mellitus, and depressive disorders.

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Section: Alzheimer’s Disease and Chronic Inflammatory Diseasesmentioning

confidence: 99%

Alzheimer’s Disease and Inflammaging

et al. 2022

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“…Increased systemic inflammation impacts many of the systems in the body including the brain, in fact, inflammation is closely associated with neuropathology (Fan et al, 2014). To date, a series of epidemiological studies have shown that MetS increases the risk of developing neurodegenerative diseases, CNS dysfunction (Islam, 2017;Motamedi et al, 2017;Ricci et al, 2017;Arshad et al, 2018;Karaca and Karaca, 2018;Palta et al, 2021), and reduced cognitive performance including deficits in memory, visuospatial abilities, executive functioning, processing speed, and overall intellectual functioning. MetS was found to be a factor of risk for: ischemic stroke, intracranial arteriosclerosis, periventricular white matter hyperintensities, and subcortical white matter lesions (Yates et al, 2012).…”

Section: From Metabolic Syndrome To Neurological Diseasesmentioning

confidence: 99%

From Metabolic Syndrome to Neurological Diseases: Role of Autophagy

Maiuolo

Gliozzi

Musolino

et al. 2021

Front. Cell Dev. Biol.

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Metabolic syndrome is not a single pathology, but a constellation of cardiovascular disease risk factors including: central and abdominal obesity, systemic hypertension, insulin resistance (or type 2 diabetes mellitus), and atherogenic dyslipidemia. The global incidence of Metabolic syndrome is estimated to be about one quarter of the world population; for this reason, it would be desirable to better understand the underlying mechanisms involved in order to develop treatments that can reduce or eliminate the damage caused. The effects of Metabolic syndrome are multiple and wide ranging; some of which have an impact on the central nervous system and cause neurological and neurodegenerative diseases. Autophagy is a catabolic intracellular process, essential for the recycling of cytoplasmic materials and for the degradation of damaged cellular organelle. Therefore, autophagy is primarily a cytoprotective mechanism; even if excessive cellular degradation can be detrimental. To date, it is known that systemic autophagic insufficiency is able to cause metabolic balance deterioration and facilitate the onset of metabolic syndrome. This review aims to highlight the current state of knowledge regarding the connection between metabolic syndrome and the onset of several neurological diseases related to it. Furthermore, since autophagy has been found to be of particular importance in metabolic disorders, the probable involvement of this degradative process is assumed to be responsible for the attenuation of neurological disorders resulting from metabolic syndrome.

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“…A recent study conducted on 350 middle-aged non-AD Hispanics suggests MetS as an arbitrary measure does not capture the risk of AD in late middle-aged men. 103 Further evaluation is needed to understand the link between MetS and the onset/progression of AD. Insulin resistance could be the bridge linking MetS and AD.…”

Section: Metabolic Dysfunctionmentioning

confidence: 99%

“…There is conflicting evidence evaluating MetS as a risk factor in AD. A recent study conducted on 350 middle‐aged non‐AD Hispanics suggests MetS as an arbitrary measure does not capture the risk of AD in late middle‐aged men 103 . Further evaluation is needed to understand the link between MetS and the onset/progression of AD.…”

Section: Hallmarks Of Neurodegenerative Diseasementioning

confidence: 99%

Hallmarks of neurodegenerative disease: A systems pharmacology perspective

Bloomingdale

Karelina

Ramakrishnan

et al. 2022

CPT Pharmacom & Syst Pharma

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Age‐related central neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are a rising public health concern and have been plagued by repeated drug development failures. The complex nature and poor mechanistic understanding of the etiology of neurodegenerative diseases has hindered the discovery and development of effective disease‐modifying therapeutics. Quantitative systems pharmacology models of neurodegeneration diseases may be useful tools to enhance the understanding of pharmacological intervention strategies and to reduce drug attrition rates. Due to the similarities in pathophysiological mechanisms across neurodegenerative diseases, especially at the cellular and molecular levels, we envision the possibility of structural components that are conserved across models of neurodegenerative diseases. Conserved structural submodels can be viewed as building blocks that are pieced together alongside unique disease components to construct quantitative systems pharmacology (QSP) models of neurodegenerative diseases. Model parameterization would likely be different between the different types of neurodegenerative diseases as well as individual patients. Formulating our mechanistic understanding of neurodegenerative pathophysiology as a mathematical model could aid in the identification and prioritization of drug targets and combinatorial treatment strategies, evaluate the role of patient characteristics on disease progression and therapeutic response, and serve as a central repository of knowledge. Here, we provide a background on neurodegenerative diseases, highlight hallmarks of neurodegeneration, and summarize previous QSP models of neurodegenerative diseases.

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Metabolic syndrome and its components in relation to in vivo brain amyloid and neurodegeneration in late middle age

Cited by 12 publications

References 37 publications

Alzheimer’s Disease and Inflammaging

Alzheimer’s Disease and Inflammaging

From Metabolic Syndrome to Neurological Diseases: Role of Autophagy

Hallmarks of neurodegenerative disease: A systems pharmacology perspective

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