Lipids and the pathogenesis of Alzheimer's disease: is there a link?
Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder characterized pathologically by amyloid-beta plaques, neurofibrillary tangles and neuronal loss. Its fundamental cause(s) and the pathological cascades leading to clinical symptoms remain unknown. Lipids and lipid peroxidation products have important roles in the homeostasis of the central nervous system. As well, lipid transport genes and vascular changes associated with peripheral dyslipidemia have been associated with an increased risk of AD. The present review discusses ways in which lipids may be involved in the pathogenesis of AD-associated neurodegeneration through their roles as neuronal structural components, cell modulators, or second messengers. Given the many possibilities through which lipids may be directly involved in or contribute to the pathogenesis of AD, the use of lipids as biomarkers for disease progression is discussed, as are other avenues for future research.
Mielke
Michelle M
MM
Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, and the Alzheimer's Disease Research Center, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA. mmielke1@jhmi.edu
Lyketsos
C G
CG
D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D000072556:Cholesterol 24-Hydroxylase; D003937:Diagnosis, Differential; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics / Q000502:physiology; D008055:Lipids / Q000502:physiology*; D008563:Membrane Lipids / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics
D001057:Apolipoproteins E; D015415:Biomarkers; D008055:Lipids; D008563:Membrane Lipids; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase