Pathways and Networks in Plasma Lipoproteins in Alzheimer's Disease
Alzheimer’s disease (AD) is the 6th leading cause of death in the United States. Currently, AD cannot be prevented or slowed, largely due to the incomplete knowledge of mechanisms. Mass spectrometry (MS) based lipidomics and proteomics have discovered novel pathways and networks in fractionated plasma lipoproteins that determine their inflammatory propensity. Pro-inflammatory plasma lipoproteins may contribute to neuroinflammation, which accelerates amyloid accumulation, neurodegeneration, and cognitive decline. These AD outcomes might be slowed down by aerobic exercise, a promising disease-modifying treatment for AD, through attenuated neuroinflammation attributable to exercise-induced anti-inflammatory propensity of plasma lipoproteins. Cholesterol is not the only contributory component in plasma lipoproteins; other lipid and protein components, such as phospholipids, sphingomyelins, and apolipoproteins, may also contribute to development of AD, and thus they may be targets for preventing or slowing down AD progression. However, no studies to date have characterized pathways and networks in plasma lipoproteins that delineate AD pathophysiology. This research will determine the relationships between plasma lipoproteins and AD pathologies (brain amyloid load and cerebral cortical volume) and functional decline (cognitive decline and incident dementia) and explore if plasma lipoproteins mediate treatment responses in older adults with AD in the FIT-AD Trial, a randomized controlled trial that studies 6-month aerobic exercise’s effects on hippocampal volume and cognition in AD.
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