Inflammation as a central mechanism in Alzheimer's disease

Kinney, Jefferson W.; Bemiller, Shane M.; Murtishaw, Andrew S.; Leisgang, Amanda M.; Salazar, Arnold; Lamb, Bruce T.

doi:10.1016/j.trci.2018.06.014

Cited by 1,591 publications

(1,307 citation statements)

References 287 publications

(333 reference statements)

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“…Wolters et al [94] have unraveled links between cerebral perfusion and the risk of dementia. A consequence of the deterioration of pericytes and loss of BBB integrity is an increased influx of immune cells into the brain, which in turn drives inflammation, an important diseasepromoting factor in neurodegenerative as well as cerebrovascular disease (for review see [100]). A decline in the number of pericytes may be observed not only in the diseased condition but may be a part of the normal aging process, as BBB breakdown and pericyte loss increase in the aging hippocampus [89].…”

Section: Neurodegenerative Diseases and The Brain Vasculature-an Emermentioning

confidence: 99%

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

2019

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Neurodegenerative and cerebrovascular diseases cause considerable human suffering, and therapy options for these two disease categories are limited or non-existing. It is an emerging notion that neurodegenerative and cerebrovascular diseases are linked in several ways, and in this review, we discuss the current status regarding vascular dysregulation in neurodegenerative disease, and conversely, how cerebrovascular diseases are associated with central nervous system (CNS) degeneration and dysfunction. The emerging links between neurodegenerative and cerebrovascular diseases are reviewed with a particular focus on pericytes-important cells that ensheath the endothelium in the microvasculature and which are pivotal for blood-brain barrier function and cerebral blood flow. Finally, we address how novel molecular and cellular insights into pericytes and other vascular cell types may open new avenues for diagnosis and therapy development for these important diseases.

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Section: Neurodegenerative Diseases and The Brain Vasculature-an Emermentioning

confidence: 99%

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

2019

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“…DHA has a significant role in the reduction of dementia risk (Schaefer et al, 2006). Neuroinflammation can be dampened by DHA supplementation in the pathogenesis of Alzheimer's disease (Kinney et al, 2018; Trépanier et al, 2016). DHA derived anti‐inflammatory eicosanoids, neuroprotectins prevent Alzheimer's disease pathogenesis (Lukiw et al, 2005).…”

Section: Roles Of Dha and Its Metabolites In Brain Functionmentioning

confidence: 99%

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

Mallick

Basak

Duttaroy

2019

Intl J of Devlp Neuroscience

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Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti-apoptotic effect, synaptic plasticity, Ca 2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n-3 fatty acids, and/or lower intake of n-6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n-3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.

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“…Consequentially, increased levels of oxidative stress that induces lipid peroxidation and mitochondrial and nuclear DNA damage have been considered as an important contributing factor to the development of age‐related diseases including AD supporting the concept of a vicious cycle where with age, accumulating dysfunctions in multiple interconnected pathways contribute to the onset and exacerbate the disease development [38,39]. Finally, a sustained inflammatory response well documented in the brain tissue of patients with AD has been considered as an early and central feature of neurodegenerative process, the “inflammation hypothesis of AD” [40]. This devastating process is not limited to the brain.…”

Section: The Rationale For the Hypothesis And Linkage To Other Majormentioning

confidence: 99%

Alzheimer's disease mechanisms in peripheral cells: Promises and challenges

Trushina¹

2019

A&D Transl Res & Clin Interv

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Introduction Development of efficacious therapeutic interventions for Alzheimer's disease (AD) is hampered by the lack of understanding early disease mechanisms, biomarkers, and models that mimic complex pathophysiology of human disease. Methods This article aims to assess to what extent peripheral cells recapitulate molecular mechanisms altered in the brain and could be used as translational models for the development of individualized medicine for AD. Results Multiple studies suggest that AD is a systemic disorder with an active crosstalk between brain and periphery where multiple pathways altered in the brain cells are also affected in plasma, cerebrospinal fluid, and other peripheral cells of AD patients. Discussion Additional studies to validate molecular mechanisms in peripheral cells using advanced system biology techniques and well‐characterized cohorts of AD patients together with the development of standardized protocols should be considered to support the application of peripheral cells in AD research.

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Inflammation as a central mechanism in Alzheimer's disease

Cited by 1,591 publications

References 287 publications

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

Alzheimer's disease mechanisms in peripheral cells: Promises and challenges

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