Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition

Abstract It is unclear how pathological aging of the inflammatory system relates to Alzheimer’s disease (AD). We tested whether age-related inflammatory changes in cerebrospinal fluid (CSF) and plasma exist across different stages of AD, and whether such changes related to AD pathology. Linear regre...

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Autores principales:	Nicholas C. Cullen, A nders Mälarstig, Erik Stomrud, Oskar Hansson, Niklas Mattsson-Carlgren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e26cbec28eb24a0890de1695b1580233
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spelling	oai:doaj.org-article:e26cbec28eb24a0890de1695b15802332021-12-02T10:49:22ZAccelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition10.1038/s41598-021-81705-72045-2322https://doaj.org/article/e26cbec28eb24a0890de1695b15802332021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81705-7https://doaj.org/toc/2045-2322Abstract It is unclear how pathological aging of the inflammatory system relates to Alzheimer’s disease (AD). We tested whether age-related inflammatory changes in cerebrospinal fluid (CSF) and plasma exist across different stages of AD, and whether such changes related to AD pathology. Linear regression was first used model chronological age in amyloid-β negative, cognitively unimpaired individuals (Aβ− CU; n = 312) based on a collection of 73 inflammatory proteins measured in both CSF and plasma. Fitted models were then applied on protein levels from Aβ+ individuals with mild cognitive impairment (Aβ+ MCI; n = 150) or Alzheimer’s disease dementia (Aβ+ AD; n = 139) to test whether the age predicted from proteins alone (“inflammatory age”) differed significantly from true chronological age. Aβ− individuals with subjective cognitive decline (Aβ− SCD; n = 125) or MCI (Aβ− MCI; n = 104) were used as an independent contrast group. The difference between inflammatory age and chronological age (InflammAGE score) was then assessed in relation to core AD biomarkers of amyloid, tau, and cognition. Both CSF and plasma inflammatory proteins were significantly associated with age in Aβ− CU individuals, with CSF-based proteins predicting chronological age better than plasma-based counterparts. Meanwhile, the Aβ− SCD and validation Aβ− CU groups were not characterized by significant inflammatory aging, while there was increased inflammatory aging in Aβ− MCI patients for CSF but not plasma inflammatory markers. Both CSF and plasma inflammatory changes were seen in the Aβ+ MCI and Aβ+ AD groups, with varying degrees of change compared to Aβ− CU and Aβ− SCD groups. Finally, CSF inflammatory changes were highly correlated with amyloid, tau, general neurodegeneration, and cognition, while plasma changes were mostly associated with amyloid and cognition. Inflammatory pathways change during aging and are specifically altered in AD, tracking closely with pathological hallmarks. These results have implications for tracking AD progression and for suggesting possible pathways for drug targeting.Nicholas C. CullenA nders MälarstigErik StomrudOskar HanssonNiklas Mattsson-CarlgrenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas C. Cullen A nders Mälarstig Erik Stomrud Oskar Hansson Niklas Mattsson-Carlgren Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition
description	Abstract It is unclear how pathological aging of the inflammatory system relates to Alzheimer’s disease (AD). We tested whether age-related inflammatory changes in cerebrospinal fluid (CSF) and plasma exist across different stages of AD, and whether such changes related to AD pathology. Linear regression was first used model chronological age in amyloid-β negative, cognitively unimpaired individuals (Aβ− CU; n = 312) based on a collection of 73 inflammatory proteins measured in both CSF and plasma. Fitted models were then applied on protein levels from Aβ+ individuals with mild cognitive impairment (Aβ+ MCI; n = 150) or Alzheimer’s disease dementia (Aβ+ AD; n = 139) to test whether the age predicted from proteins alone (“inflammatory age”) differed significantly from true chronological age. Aβ− individuals with subjective cognitive decline (Aβ− SCD; n = 125) or MCI (Aβ− MCI; n = 104) were used as an independent contrast group. The difference between inflammatory age and chronological age (InflammAGE score) was then assessed in relation to core AD biomarkers of amyloid, tau, and cognition. Both CSF and plasma inflammatory proteins were significantly associated with age in Aβ− CU individuals, with CSF-based proteins predicting chronological age better than plasma-based counterparts. Meanwhile, the Aβ− SCD and validation Aβ− CU groups were not characterized by significant inflammatory aging, while there was increased inflammatory aging in Aβ− MCI patients for CSF but not plasma inflammatory markers. Both CSF and plasma inflammatory changes were seen in the Aβ+ MCI and Aβ+ AD groups, with varying degrees of change compared to Aβ− CU and Aβ− SCD groups. Finally, CSF inflammatory changes were highly correlated with amyloid, tau, general neurodegeneration, and cognition, while plasma changes were mostly associated with amyloid and cognition. Inflammatory pathways change during aging and are specifically altered in AD, tracking closely with pathological hallmarks. These results have implications for tracking AD progression and for suggesting possible pathways for drug targeting.
format	article
author	Nicholas C. Cullen A nders Mälarstig Erik Stomrud Oskar Hansson Niklas Mattsson-Carlgren
author_facet	Nicholas C. Cullen A nders Mälarstig Erik Stomrud Oskar Hansson Niklas Mattsson-Carlgren
author_sort	Nicholas C. Cullen
title	Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition
title_short	Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition
title_full	Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition
title_fullStr	Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition
title_full_unstemmed	Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition
title_sort	accelerated inflammatory aging in alzheimer’s disease and its relation to amyloid, tau, and cognition
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e26cbec28eb24a0890de1695b1580233
work_keys_str_mv	AT nicholasccullen acceleratedinflammatoryaginginalzheimersdiseaseanditsrelationtoamyloidtauandcognition AT andersmalarstig acceleratedinflammatoryaginginalzheimersdiseaseanditsrelationtoamyloidtauandcognition AT erikstomrud acceleratedinflammatoryaginginalzheimersdiseaseanditsrelationtoamyloidtauandcognition AT oskarhansson acceleratedinflammatoryaginginalzheimersdiseaseanditsrelationtoamyloidtauandcognition AT niklasmattssoncarlgren acceleratedinflammatoryaginginalzheimersdiseaseanditsrelationtoamyloidtauandcognition
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Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition

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