Inflammation, negative affect, and amyloid burden in Alzheimer’s disease: Insights from the kynurenine pathway

Willette, Auriel A.; Pappas, Colleen; Hoth, Nathan; Wang, Qian; Klinedinst, Brandon S.; Willette, Sara A; Larsen, Brittany; Pollpeter, Amy; Li, Tianqi; Le, Scott T.; Collazo-Martinez, Ana D.; Mochel, Jonathan P.; Allenspach, Karin; Dantzer, Robert

doi:10.1016/j.bbi.2021.03.019

Cited by 33 publications

(27 citation statements)

References 73 publications

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“…Patients with normal cognition, MCI, and AD were assessed in a clinical study for KYN, L-TRP, and 5-HT in serum, A β , and tau and KYN in CSF. An inflammatory signal cascade may occur during AD, related to the increase in KYN [ 181 ]. Higher K/T ratios were associated with many inflammatory markers and lower functional independence and memory scores.…”

Section: Kp Metabolites As Biomarkers In Admentioning

confidence: 99%

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Kynurenine Pathway Metabolites as Biomarkers in Alzheimer’s Disease

Liang

Xie

et al. 2022

Disease Markers

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that deteriorates cognitive function. Patients with AD generally exhibit neuroinflammation, elevated beta-amyloid (Aβ), tau phosphorylation (p-tau), and other pathological changes in the brain. The kynurenine pathway (KP) and several of its metabolites, especially quinolinic acid (QA), are considered to be involved in the neuropathogenesis of AD. The important metabolites and key enzymes show significant importance in neuroinflammation and AD. Meanwhile, the discovery of changed levels of KP metabolites in patients with AD suggests that KP metabolites may have a prominent role in the pathogenesis of AD. Further, some KP metabolites exhibit other effects on the brain, such as oxidative stress regulation and neurotoxicity. Both analogs of the neuroprotective and antineuroinflammation metabolites and small molecule enzyme inhibitors preventing the formation of neurotoxic and neuroinflammation compounds may have potential therapeutic significance. This review focused on the KP metabolites through the relationship of neuroinflammation in AD, significant KP metabolites, and associated molecular mechanisms as well as the utility of these metabolites as biomarkers and therapeutic targets for AD. The objective is to provide references to find biomarkers and therapeutic targets for patients with AD.

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Section: Kp Metabolites As Biomarkers In Admentioning

confidence: 99%

“…Higher K/T ratios were associated with many inflammatory markers and lower functional independence and memory scores. A β and complement systems may be key contributing factors in this process [ 181 ].…”

Section: Kp Metabolites As Biomarkers In Admentioning

confidence: 99%

Kynurenine Pathway Metabolites as Biomarkers in Alzheimer’s Disease

Liang

Xie

et al. 2022

Disease Markers

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“…Quinolinic acid is up-regulated in AD patient brain tissue which is important since quinolinic acid causes lipid peroxidation and is neurotoxic (via activity as a N-methyl D-aspartate (NMDA) receptor agonist) (Guillemin et al, 2005). Additionally, another study reports that the kynurenine/tryptophan ratio is associated with inflammation and impaired memory in humans (Willette et al, 2021). Clearly, the impact of metabolites in the kynurenine pathway on AD is complex (and likely depends on the specific metabolite) highlighting the need for additional studies.…”

Section: Bacterial Metabolitesmentioning

confidence: 99%

Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites

et al. 2021

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Alzheimer’s disease (AD) is a neurodegenerative disease that impacts 45 million people worldwide and is ranked as the 6th top cause of death among all adults by the Centers for Disease Control and Prevention. While genetics is an important risk factor for the development of AD, environment and lifestyle are also contributing risk factors. One such environmental factor is diet, which has emerged as a key influencer of AD development/progression as well as cognition. Diets containing large quantities of saturated/trans-fats, refined carbohydrates, limited intake of fiber, and alcohol are associated with cognitive dysfunction while conversely diets low in saturated/trans-fats (i.e., bad fats), high mono/polyunsaturated fats (i.e., good fats), high in fiber and polyphenols are associated with better cognitive function and memory in both humans and animal models. Mechanistically, this could be the direct consequence of dietary components (lipids, vitamins, polyphenols) on the brain, but other mechanisms are also likely to be important. Diet is considered to be the single greatest factor influencing the intestinal microbiome. Diet robustly influences the types and function of micro-organisms (called microbiota) that reside in the gastrointestinal tract. Availability of different types of nutrients (from the diet) will favor or disfavor the abundance and function of certain groups of microbiota. Microbiota are highly metabolically active and produce many metabolites and other factors that can affect the brain including cognition and the development and clinical progression of AD. This review summarizes data to support a model in which microbiota metabolites influence brain function and AD.

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“…Persistent inflammation can lead to the chronic phase [ 65 ]. Chronic inflammation contributes to immune diseases [ 66 ], arthritis, diabetes, cancer [ 67 ], cardiovascular and neurodegenerative diseases [ 8 , 68 ] and many other chronic diseases [ 69 , 70 , 71 ].…”

Section: Role Of Punicalagin In Inflammation-associated Diseasesmentioning

confidence: 99%

Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases

Cao

Liu

et al. 2021

Antioxidants

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Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is considered to be the major active component of pomegranate extracts. In this review we have focused on recent studies into the therapeutic effects of punicalagin on inflammation-associated chronic diseases and the regulatory roles in NF-κB, MAPK, IL-6/JAK/STAT3 and PI3K/Akt/mTOR signaling pathways. We have concluded that punicalagin may be a promising therapeutic compound in preventing and treating inflammation-associated chronic diseases, although further clinical studies are required.

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Inflammation, negative affect, and amyloid burden in Alzheimer’s disease: Insights from the kynurenine pathway

Cited by 33 publications

References 73 publications

Kynurenine Pathway Metabolites as Biomarkers in Alzheimer’s Disease

Kynurenine Pathway Metabolites as Biomarkers in Alzheimer’s Disease

Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites

Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases

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