Dataset Information

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

ABSTRACT:

Background

Depressive symptoms in Alzheimer's disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression inflammatory processes are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed associations between Kyn and behavioral, neuroanatomical, neuropathological, and physiological outcomes common to both AD and negative affect across the AD continuum.

Methods

In 58 cognitively normal, 396 mild cognitive impairment, and 112 AD participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI1) cohort, serum markers of 5-HT, tryptophan, and Kyn were measured and their relationships investigated with immunologic markers, affect and functional outcomes, CSF markers of beta-amyloid (Aβ) and tau, and regional gray matter.

Results

A higher Kyn/Tryptophan ratio was linked to many inflammatory markers, as well as lower functional independence and memory scores. A higher Kyn/5-HT ratio showed similar associations, but also strong relationships with negative affect and neuropsychiatric disturbance, executive dysfunction, and global cognitive decline. Further, gray matter atrophy was seen in hippocampus, anterior cingulate, and prefrontal cortices, as well as greater amyloid and total tau deposition. Finally, using moderated-mediation, several pro-inflammatory factors partially mediated Kyn/5-HT and negative affect scores in participants with subclinical Aβ (i.e., Aβ-), whereas such associations were fully mediated by Complement 3 in Aβ+ participants.

Conclusion

These findings suggest that inflammatory signaling cascades may occur during AD, which is associated with increased Kyn metabolism that influences the pathogenesis of negative affect. Aβ and the complement system may be critical contributing factors in this process.

SUBMITTER: Willette AA

PROVIDER: S-EPMC8187283 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Willette Auriel A AA Pappas Colleen C Hoth Nathan N Wang Qian Q Klinedinst Brandon B Willette Sara A SA Larsen Brittany B Pollpeter Amy A Li Tianqi T Le Scott S Collazo-Martinez Ana D AD Mochel Jonathan P JP Allenspach Karin K Dantzer Robert R

Brain, behavior, and immunity 20210326

<h4>Background</h4>Depressive symptoms in Alzheimer's disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression inflammatory processes are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed associations between Kyn and behavioral, neuroanatomical, neuropathological, and physiological outcomes common to both AD and negative affect across the AD continuum.<h ...[more]

PMID: 33775832

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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