Daniela Mariosa1, Niklas Hammar2, Håkan Malmström3, Caroline Ingre4, Ingmar Jungner3, Weimin Ye1, Fang Fang1, Göran Walldius5. 1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 2. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden and Global Medical Affairs, AstraZeneca, Mölndal, Sweden. 3. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 5. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract
OBJECTIVE: To assess the associations of blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms with the future risk of amyotrophic lateral sclerosis (ALS). METHODS: In the Apolipoprotein-related MOrtality RISk study, we enrolled 636,132 men and women during 1985-1996 in Stockholm, Sweden, with measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Serum low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were either directly measured or calculated from total cholesterol, triglycerides, and apoA-I. The cohort was followed until the end of 2011. We used Cox models and mixed-effects models to, first, estimate the associations between these biomarkers and ALS incidence and, second, to assess the changes of these biomarkers during the 20 years before ALS diagnosis. RESULTS: One-unit increase of LDL-C (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.02-1.27), apoB (HR = 1.68; 95% CI = 1.17-2.42), and apoB/apoA-I ratio (HR = 1.90; 95% CI = 1.29-2.78) was associated with a higher incidence of ALS. High glucose level (≥6.11mmol/L) was associated with a lower incidence (HR = 0.62; 95% CI = 0.42-0.93), whereas high LDL-C/HDL-C (≥3.50; HR = 1.50; 95% CI = 1.15-1.96) and high apoB/apoA-I (≥0.90 for men, ≥0.8 for women; HR = 1.41; 95% CI = 1.04-1.90) ratios were associated with a higher incidence. During the 10 years before diagnosis, ALS patients had increasing levels of LDL-C, HDL-C, apoB, and apoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios. INTERPRETATION: Alterations in the carbohydrate, lipid, and apolipoprotein metabolisms are associated with ALS risk and may serve as prodromal symptoms decades before ALS diagnosis. The imbalance between apoB and apoA-I as well as between LDL-C and HDL-C may be an etiological mechanism for ALS and needs to be further studied. Ann Neurol 2017;81:718-728.
OBJECTIVE: To assess the associations of blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms with the future risk of amyotrophic lateral sclerosis (ALS). METHODS: In the Apolipoprotein-related MOrtality RISk study, we enrolled 636,132 men and women during 1985-1996 in Stockholm, Sweden, with measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Serum low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were either directly measured or calculated from total cholesterol, triglycerides, and apoA-I. The cohort was followed until the end of 2011. We used Cox models and mixed-effects models to, first, estimate the associations between these biomarkers and ALS incidence and, second, to assess the changes of these biomarkers during the 20 years before ALS diagnosis. RESULTS: One-unit increase of LDL-C (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.02-1.27), apoB (HR = 1.68; 95% CI = 1.17-2.42), and apoB/apoA-I ratio (HR = 1.90; 95% CI = 1.29-2.78) was associated with a higher incidence of ALS. High glucose level (≥6.11mmol/L) was associated with a lower incidence (HR = 0.62; 95% CI = 0.42-0.93), whereas high LDL-C/HDL-C (≥3.50; HR = 1.50; 95% CI = 1.15-1.96) and high apoB/apoA-I (≥0.90 for men, ≥0.8 for women; HR = 1.41; 95% CI = 1.04-1.90) ratios were associated with a higher incidence. During the 10 years before diagnosis, ALSpatients had increasing levels of LDL-C, HDL-C, apoB, and apoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios. INTERPRETATION: Alterations in the carbohydrate, lipid, and apolipoprotein metabolisms are associated with ALS risk and may serve as prodromal symptoms decades before ALS diagnosis. The imbalance between apoB and apoA-I as well as between LDL-C and HDL-C may be an etiological mechanism for ALS and needs to be further studied. Ann Neurol 2017;81:718-728.
Authors: Hiroshi Mitsumoto; Diana C Garofalo; Regina M Santella; Eric J Sorenson; Björn Oskarsson; J Americo M Fernandes; Howard Andrews; Jonathan Hupf; Madison Gilmore; Daragh Heitzman; Richard S Bedlack; Jonathan S Katz; Richard J Barohn; Edward J Kasarskis; Catherine Lomen-Hoerth; Tahseen Mozaffar; Sharon P Nations; Andrea J Swenson; Pam Factor-Litvak Journal: Amyotroph Lateral Scler Frontotemporal Degener Date: 2020-04-10 Impact factor: 4.092
Authors: James C Dodge; Elizabeth H Jensen; Jinlong Yu; S Pablo Sardi; Allison R Bialas; Tatyana V Taksir; Dinesh S Bangari; Lamya S Shihabuddin Journal: J Neurosci Date: 2020-10-13 Impact factor: 6.167
Authors: Colin J Mahoney; Rebekah M Ahmed; William Huynh; Sicong Tu; Jonathan D Rohrer; Richard S Bedlack; Orla Hardiman; Matthew C Kiernan Journal: CNS Drugs Date: 2021-05-15 Impact factor: 5.749
Authors: Kjetil Bjornevik; Éilis J O'Reilly; Marianna Cortese; Jeremy D Furtado; Laurence N Kolonel; Loic Le Marchand; Marjorie L Mccullough; Sabrina Paganoni; Michael A Schwarzschild; Aladdin H Shadyab; Joann E Manson; Alberto Ascherio Journal: Amyotroph Lateral Scler Frontotemporal Degener Date: 2020-09-28 Impact factor: 4.092