University of Oulu

Chaiyasit Sittiwet, Piia Simonen, Markku J. Nissinen, Helena Gylling, Timo E. Strandberg, Serum noncholesterol sterols in Alzheimer's disease: the Helsinki Businessmen Study, Translational Research, Volume 202, 2018, Pages 120-128, ISSN 1931-5244, https://doi.org/10.1016/j.trsl.2018.07.002

Serum noncholesterol sterols in Alzheimer's disease : the Helsinki businessmen study

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Author: Sittiwet, Chaiyasit1,2; Simonen, Piia3; Nissinen, Markku J.1;
Organizations: 1University of Helsinki and Helsinki University Hospital, Abdominal Center, Gastroenterology, 00029 HUS, Helsinki, Finland
2Faculty of Medicine, Mahasarakham University, Khamreung, Kantharawichai, Mahasarakham, Thailand
3University of Helsinki and Helsinki University Hospital, Heart and Lung Center, Cardiology, 00029 HUS, Helsinki, Finland
4University of Helsinki and Helsinki University Hospital, Internal Medicine, 00029 HUS, Helsinki, Finland
5University of Helsinki, Clinicum, and Helsinki University Hospital, 00029 HUS, Helsinki, Finland
6University of Oulu, Center for Life Course Health Research, Oulu, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2019042413185
Language: English
Published: Elsevier, 2018
Publish Date: 2019-07-26
Description:

Abstract

Cerebral cholesterol metabolism is perturbed in late-onset Alzheimer’s disease (AD), but whether also the extracerebral cholesterol metabolism is perturbed is not known. Thus, we studied whole-body cholesterol synthesis and absorption with serum noncholesterol sterols in men without AD (n = 114) or with (n = 18) "pure" AD (no concomitant atherosclerotic cardiovascular disease) in a long-term cohort (the Helsinki Businessmen Study) of home-dwelling older men without lipid-lowering drugs and on their habitual home diet. Serum lipids did not differ between AD and controls, but age was higher (78 ± 1 vs 74 ± 0.3 years, mean ± standard error, P < 0.001), age-adjusted plasma glucose concentration was lower (4.8 ± 0.3 vs 5.7 ± 0.1 mmol/L, P = 0.011), and APOE ε4 allele and frailty were more frequent in AD than in controls. Of the age and frailty-adjusted serum noncholesterol sterols desmosterol and lathosterol ratios to cholesterol reflecting cholesterol synthesis were lower in AD than in controls (eg, lathosterol 114 ± 12 vs 137 ± 5 10² µmol/mmol cholesterol, P = 0.004). Cholestanol ratio to cholesterol was higher in AD than in controls suggesting increased cholesterol absorption. lathosterol/sitosteroll ratio reflecting cholesterol metabolism was lower in AD than in controls (0.95 ± 0.28 vs 1.52 ± 0.11 10² µmol/mmol cholesterol, P = 0.027). In AD, plasma glucose correlated negatively with cholesterol synthesis, whereas in controls the correlation was positive. In conclusion, extracerebral cholesterol metabolism was altered in AD. This finding along with the low plasma glucose concentration and its paradoxical interaction with cholesterol synthesis opens new perspectives in the regulation of cholesterol metabolism and glucose homeostasis in AD.

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Series: Translational research
ISSN: 1931-5244
ISSN-E: 1878-1810
ISSN-L: 1931-5244
Volume: 202
Pages: 120 - 128
DOI: 10.1016/j.trsl.2018.07.002
OADOI: https://oadoi.org/10.1016/j.trsl.2018.07.002
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: This research was supported by the Helsinki University Hospital (TYH2014245 and TYH2015211), and the Academy of Finland (grant 311492).
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/