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 Tybjaerg-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 Tybjaerg-Hansen, Ruth Frikke-Schmidt^*

^*Corresponding author af dette arbejde

30 Citationer (Scopus)

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 : the journal of the Alzheimer's Association
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 - nov. 2022

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Hegazy, S. H., Thomassen, J. Q., Rasmussen, I. J., Nordestgaard, B. G., Tybjaerg-Hansen, A., & Frikke-Schmidt, R. (2022). C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population. Alzheimer's & dementia : the journal of the Alzheimer's Association, 18(11), 2262-2271. https://doi.org/10.1002/alz.12568

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 et al.
I: Alzheimer's & dementia : the journal of the Alzheimer's Association, Bind 18, Nr. 11, 11.2022, s. 2262-2271.

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

Hegazy, SH, Thomassen, JQ, Rasmussen, IJ, Nordestgaard, BG , Tybjaerg-Hansen, A & Frikke-Schmidt, R 2022, 'C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population', Alzheimer's & dementia : the journal of the Alzheimer's Association, bind 18, nr. 11, s. 2262-2271. https://doi.org/10.1002/alz.12568

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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 - Nordestgaard, Børge G

AU - Tybjaerg-Hansen, Anne

AU - Frikke-Schmidt, Ruth

PY - 2022/11

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N2 - 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.

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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KW - CRP

KW - C-reactive protein

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KW - gene–environment interaction

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

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