Low-Density Lipoprotein Particle Size Subfractions and Cerebral Amyloidosis

Autor: Sung Lee, Bruce R Reed, Trusha Parekh, Hussein N. Yassine, Helena C. Chui, Ronald M. Krauss, Sarah M. King
Rok vydání: 2019
Předmět:
0301 basic medicine
Apolipoprotein E
Male
medicine.medical_specialty
Apolipoprotein B
Neuroimaging
Neuropsychological Tests
Hippocampus
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Apolipoproteins E
Internal medicine
medicine
Humans
Particle Size
Triglycerides
Aged
Aged
80 and over
Brain Diseases
biology
Triglyceride
Chemistry
Cholesterol
General Neuroscience
General Medicine
Amyloidosis
Cholesterol
LDL
medicine.disease
LRP1
Magnetic Resonance Imaging
Lipoproteins
LDL
Psychiatry and Mental health
Clinical Psychology
030104 developmental biology
Endocrinology
Positron-Emission Tomography
LDL receptor
biology.protein
lipids (amino acids
peptides
and proteins)
Geriatrics and Gerontology
Low-density lipoprotein particle
030217 neurology & neurosurgery
Dyslipidemia
Biomarkers
Zdroj: Journal of Alzheimer's disease : JAD. 68(3)
ISSN: 1875-8908
Popis: Cerebral beta-amyloidosis (CA) is a condition in which amyloid-β (Aβ) proteins are deposited in the cerebral cortex and is a predictor of Alzheimer's disease (AD). The Aging Brain Study (ABS) investigated risk factors for CA in persons with diabetes and dyslipidemia. In the ABS, we identified that greater levels of LDL cholesterol and lower levels of HDL cholesterol were associated with increased CA. LDL particles comprise multiple species of varying size, density, and protein composition. For example, within a lipoprotein profile characteristic for persons with obesity and diabetic dyslipidemia, larger LDL particles have a greater ApoE to ApoB ratio, enhancing their binding affinity to LDL receptors. The goal of this study was to identify LDL particles that associate with CA in ABS. LDL particle size fractions were measured by ion mobility in plasma samples of 58 participants (40 women and 18 men). CA was assessed using Pittsburgh Compound B index-Positron Emission Tomography (PiB-PET) imaging. Among the LDL subfractions, greater plasma levels of large LDL particles were significantly associated with greater cerebral amyloidosis and lower hippocampal volumes independent of LDL cholesterol or triglyceride levels. Since Aβ is cleared by the LDL receptor family, such as lipoprotein-like receptor 1 (LRP1), one potential mechanism for our findings is competition between ApoE enriched larger LDL particles and brain-derived Aβ on hepatic Aβ clearance and degradation. We conclude that assessing larger LDL particles in persons with atherogenic dyslipidemia may provide a mechanistic biomarker for the extent of CA.
Databáze: OpenAIRE
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