Decreased plasma C-reactive protein levels in APOE ε 4 allele carriers

Henna Martiskainen; Mari Takalo; Alina Solomon; Alena Stančáková; Mikael Marttinen; Teemu Natunen; Annakaisa Haapasalo; Sanna-Kaisa Herukka; Johanna Kuusisto; Hilkka Soininen; Miia Kivipelto; Markku Laakso; Mikko Hiltunen

doi:10.1002/acn3.639

Decreased plasma C-reactive protein levels in APOE ε 4 allele carriers

Ann Clin Transl Neurol. 2018 Sep 17;5(10):1229-1240. doi: 10.1002/acn3.639. eCollection 2018 Oct.

Authors

Henna Martiskainen¹, Mari Takalo², Alina Solomon^{3

4}, Alena Stančáková¹, Mikael Marttinen², Teemu Natunen², Annakaisa Haapasalo⁵, Sanna-Kaisa Herukka^{3

6}, Johanna Kuusisto^{1

7}, Hilkka Soininen^{3

6}, Miia Kivipelto^{3

4

8}, Markku Laakso^{1

7}, Mikko Hiltunen²

Affiliations

¹ Institute of Clinical Medicine Internal Medicine University of Eastern Finland P.O. Box 1627 Kuopio 70211 Finland.
² Institute of Biomedicine University of Eastern Finland Yliopistonranta 1 E, P.O. Box 1627 Kuopio 70211 Finland.
³ Department of Neurology Institute of Clinical Medicine University of Eastern Finland P.O. Box 1627 Kuopio 70211 Finland.
⁴ Division of Clinical Geriatrics Center for Alzheimer Research NVS, Karolinska Institutet Novum 5th floor Huddinge 14157 Sweden.
⁵ A.I Virtanen Institute for Molecular Sciences University of Eastern Finland Neulaniementie 2 Kuopio 70211 Finland.
⁶ Neurocenter Neurology Kuopio University Hospital Kuopio Finland.
⁷ Kuopio University Hospital Kuopio Finland.
⁸ Department of Public Health Solutions Public Health Promotion Unit National Institute for Health and Welfare PO Box 30 Helsinki 00271 Finland.

Abstract

Objective: Apolipoprotein E (APOE) ε4 allele is a well-established risk factor in Alzheimer's disease (AD). Here, we assessed the effects of APOE polymorphism on cardiovascular, metabolic, and inflammation-related parameters in population-based cohorts.

Methods: Association of cardiovascular, metabolic, and inflammation-related parameters with the APOE polymorphism in a large Finnish Metabolic Syndrome in Men (METSIM) cohort and Finnish Geriatric Intervention study to prevent cognitive impairment and disability (FINGER) were investigated. Brain-specific effects were addressed in postmortem brain samples.

Results: Individuals carrying the APOE ε4 allele displayed significantly elevated serum/plasma LDL cholesterol and apolipoprotein B levels. APOE ε3ε4 and ε4ε4 significantly associated with lower levels of plasma high-sensitivity C-reactive protein (hs-CRP). Plasma amyloid-β 42 (Aβ42) and reduced hs-CRP levels showed an association independently of the APOE status.

Interpretation: These data suggest that the APOE ε4 allele associates with lower levels of hs-CRP in individuals without dementia. Moreover, Aβ42 may encompass anti-inflammatory effects reflected by reduced hs-CRP levels.

Grants and funding

This work was funded by Academy of Finland grants 307866, 278457, 287490, and 294061; Sigrid Jusélius Foundation grant ; Strategic Neuroscience Funding of the University of Eastern Finland grant 601055; VPH Dementia Research Enabled by IT VPH‐DARE@IT grant ; EADB project in the JPND‐CO‐FUND program grant 301220; SynaNet grant 692340; Swedish Research Council grant ; Alzheimerfonden Sweden grant ; Center for Innovative Medicine (CIMED) at Karolinska Institutet grant ; Knut and Alice Wallenberg Foundation grant ; Konung Gustaf V:s och Drottning Victorias Frimurarstiftelse grant ; Stockholm County Council (ALF) grant ; Stockholms sjukhem grant ; Joint Program of Neurodegenerative Disorders – prevention grant .