Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

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T1 - Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

AU - Nägga, Katarina

AU - Gustavsson, Anna-Märta

AU - Stomrud, Erik

AU - Lindqvist, Daniel

AU - van Westen, Danielle

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Melander, Olle

AU - Hansson, Oskar

PY - 2018/1/2

Y1 - 2018/1/2

N2 - Objective To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.Methods This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.Results CSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03–1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10–1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.Conclusions Increased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

AB - Objective To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.Methods This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.Results CSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03–1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10–1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.Conclusions Increased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

U2 - 10.1212/WNL.0000000000004749

DO - 10.1212/WNL.0000000000004749

M3 - Article

VL - 90

SP - 1

EP - 11

JO - Neurology

T2 - Neurology

JF - Neurology

SN - 1526-632X

IS - 1

ER -