Sharif H Hegazy1, Jesper Qvist Thomassen1, Ida Juul Rasmussen1, Børge G Nordestgaard2,3,4,5, Anne Tybjaerg-Hansen1,2,4,5, Ruth Frikke-Schmidt1,2,5. 1. Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. 2. The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark. 3. Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark. 4. The Copenhagen City Heart Study, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Frederiksberg, Denmark. 5. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
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.
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.
Authors: Marios K Georgakis; Rainer Malik; Tom G Richardson; Joanna M M Howson; Christopher D Anderson; Stephen Burgess; G Kees Hovingh; Martin Dichgans; Dipender Gill Journal: BMC Med Date: 2022-08-11 Impact factor: 11.150