This article evaluates recent experimental and human evidence regarding the involvement of lipids, lipoproteins, and apolipoproteins in neurodegenerative diseases, and reviews the current literature of the effects of cholesterol-lowering treatment on cognition.
Plasma levels of traditional lipids and lipoproteins are not consistently associated with risk of dementia even though low plasma levels of apolipoprotein E, through unknown mechanisms, robustly predict future dementia. Experimental evidence suggests neuroprotective roles of several brain and cerebrospinal fluid apolipoproteins. Whether plasma levels of apolipoprotein E, or any other apolipoprotein with possible central nervous system and/or blood–brain barrier functions (apolipoproteins J, A-I, A-II, A-IV, D, C-I, and C-III) may become accessible biomarker components that improve risk prediction for dementia together with genetic risk variants and cardiovascular risk factors remains to be determined.
Apolipoproteins with well established functions in peripheral lipid metabolism may play important roles for brain vascular health and Alzheimer's disease pathophysiology. Experimental work on lipids, lipoproteins, and apolipoproteins in the central nervous system together with robust prospective human studies will help to substantiate the drug target potential of these lipid components.
aDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
bDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals
cFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Correspondence to Ruth Frikke-Schmidt, Chief Physician, Associate Professor, Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: firstname.lastname@example.org.