Cholesterol, 24-Hydroxycholesterol, and 27-Hydroxycholesterol as Surrogate Biomarkers in Cerebrospinal Fluid in Mild Cognitive Impairment and Alzheimer’s Disease: A Meta-Analysis

Article type: Research Article

Authors: Wang, Hua-Long^{a; 1} | Wang, Yan-Yong^{a; 1} | Liu, Xin-Gang^b | Kuo, Sheng-Han^c | Liu, Na^a | Song, Qiao-Yun^{d; *} | Wang, Ming-Wei^{a; e; *}

Affiliations: [a] Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China | [b] Department of Rehabilitation, Jingxing Hospital, Jingxing, Hebei, PR China | [c] Department of Neurology, Columbia University, New York, NY, USA | [d] Department of Reproductive Genetics, Hebei General Hospital, Shijiazhuang, Hebei, PR China | [e] Brain Aging and Cognitive Neuroscience Laboratory of Hebei province, Shijiazhuang, Hebei, PR China

Correspondence: [*] Correspondence to: Ming-Wei Wang, Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei, PR China. E-mail: [email protected].

Correspondence: [*] Correspondence to: Qiao-Yun Song, Department of Reproductive Genetics, Hebei General Hospital, Shijiazhuang 050051, Hebei, PR China. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Abnormal cholesterol metabolism is an established feature of Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) is the fluid surrounding the central nervous system, and the protein and lipid content alterations in the CSF could be biomarkers for degenerative changes in the brain. The laboratory diagnosis of AD is limited to the analysis of three biomarkers in CSF: Aβ42, total tau, and phospho-tau. The purpose of this analysis is to systematically analyze the available data describing the biomarkers of cholesterol and its metabolites in the CSF of subjects with AD. MEDLINE, EMBASE, and the Cochrane Central database were systematically queried to collect studies that have evaluated the markers of cholesterol and its metabolites in the CSF of subjects with mild cognitive impairment (MCI) or AD and age-matched controls. Analysis of the published data shows that the levels of cholesterol are increased in MCI subjects; 24-hydroxycholesterol and 27-hydroxycholesterol are elevated in AD and MCI subjects compared to controls. There is a significant dysfunction of cholesterol metabolism in the CSF of AD subjects. This analysis indicates that in addition to the available biomarkers in the CSF, such as Aβ42, total tau, and phospho-tau, 24-hydroxycholesterol, 27-hydroxycholesterol, and cholesterol appear to be sensitive biomarkers for the evaluation of MCI and AD.

Keywords: Alzheimer’s disease, cerebrospinal fluid, cholesterol, 24-hydroxycholesterol, 27-hydroxycholesterol

DOI: 10.3233/JAD-150734

Journal: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 45-55, 2016