C-reactive protein levels and risk of dementia — Observational and genetic studies of 111,242 individuals from the general population

Sharif H. Hegazy; Jesper Qvist Thomassen; Ida Juul Rasmussen; Børge G. Nordestgaard; Anne Tybjærg-Hansen; Ruth Frikke-Schmidt

doi:10.1002/alz.12568

C-reactive protein levels and risk of dementia — Observational and genetic studies of 111,242 individuals from the general population

Sharif H. Hegazy, Jesper Qvist Thomassen, Ida Juul Rasmussen, Børge G. Nordestgaard, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

27 Citationer (Scopus)

13 Downloads (Pure)

Abstract

Introduction: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear. Methods: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined. Results: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29–2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m² (P = 4 × 10⁻⁶). Discussion: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.

Originalsprog	Engelsk
Tidsskrift	Alzheimer's & Dementia
Vol/bind	18
Udgave nummer	11
Sider (fra-til)	2262-2271
Antal sider	10
ISSN	1552-5260
DOI	https://doi.org/10.1002/alz.12568
Status	Udgivet - 2022

Bibliografisk note

Funding Information:
We thank the participants of the Copenhagen General Population Study and the Copenhagen City Heart Study for their important contributions. This work was supported by the Lundbeck Foundation (grant no. R278‐2018‐804), the Danish Heart Foundation, and the Independent Research Fund Denmark (stipend and travelgrants). The funding bodies had no roles in the design of the study; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
Alzheimer's & Dementia© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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10.1002/alz.12568Licens: CC BY-NC-ND

FulltextForlagets udgivne version, 0,98 MBLicens: CC BY-NC-ND

Citationsformater

C-reactive protein levels and risk of dementia — Observational and genetic studies of 111,242 individuals from the general population. / Hegazy, Sharif H.; Thomassen, Jesper Qvist; Rasmussen, Ida Juul; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne ; Frikke-Schmidt, Ruth.

I: Alzheimer's & Dementia, Bind 18, Nr. 11, 2022, s. 2262-2271.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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abstract = "Introduction: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear. Methods: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined. Results: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29–2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m2 (P = 4 × 10−6). Discussion: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.",

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AU - Hegazy, Sharif H.

AU - Thomassen, Jesper Qvist

AU - Rasmussen, Ida Juul

AU - Nordestgaard, Børge G.

AU - Tybjærg-Hansen, Anne

AU - Frikke-Schmidt, Ruth

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AB - Introduction: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear. Methods: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined. Results: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29–2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m2 (P = 4 × 10−6). Discussion: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.

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