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

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Cullen, Nicholas C.Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups (author)

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

Article/chapterEnglish2021

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2021-01-21
Springer Science and Business Media LLC,2021

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LIBRIS-ID:oai:lup.lub.lu.se:f6c38995-eb40-438f-9293-de5c38812e01
https://lup.lub.lu.se/record/f6c38995-eb40-438f-9293-de5c38812e01URI
https://doi.org/10.1038/s41598-021-81705-7DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:145957648URI

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Language:English
Summary in:English

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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.

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MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng

Added entries (persons, corporate bodies, meetings, titles ...)

Mälarstig, AndersKarolinska Institutet,Karolinska Institute,Pfizer Sweden (author)
Stomrud, ErikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-esr (author)
Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (author)
Mattsson-Carlgren, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-nmn (author)
Klinisk minnesforskningForskargrupper vid Lunds universitet (creator_code:org_t)

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