Serum 24‐hydroxycholesterol in probable Alzheimer's dementia: Reexploring the significance of a tentative Alzheimer's disease biomarker

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractObjective: This study measured and analyzed the serum levels of 24-hydroxycholesterol in patients with probable Alzheimer's disease (AD) and age-/sex-matched controls. Methods:A case-control study involving 40 AD patients and 40 controls was performed at a tertiary neurological teaching hospital in eastern India. Blood and serum samples were collected for APOE genotyping and 24-hydroxycholesterol levels, respectively.Results: Serum 24-hydroxycholesterol was significantly lower in AD patients compared to controls (median concentration: controls, 47.14 ng/mL (interquartile range, 16.34); AD patients, 32.93 ng/mL (interquartile range, 9.45); P < 0.001) but showed no significant correlation with Mini Mental State Examination (MMSE) score in AD cases (r = −0.169, P = 0.298) or in controls (r = 0.18, P = 0.26). No statistically significant difference was observed between serum 24-hydroxycholesterol levels of the APOE4-positive and -negative subgroups in AD patients (P = 0.79). Findings were consistent and unchanged even when the ratio of serum 24-hydroxycholesterol to serum total cholesterol was considered. Conclusion:The decreased 24-hydroxycholesterol level in peripheral circulation in AD cases observed in the present study may suggest its role in AD pathogenesis.The lack of a clear correlation between serum levels of 24-hydroxycholesterol and MMSE score-a surrogate marker of AD severity-raises the question as to whether 24-hydroxycholesterol level declines with decreasing neuronal mass or whether the steroid continues to play a protective role. K E Y W O R D S 24-hydroxycholesterol, Alzheimer's dementia, APOE, biomarkers, case-control, India | 75 ROY et al.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…However, standard imaging methods (i.e., PET or MRI) are not suitable for lipid detection, and brain biopsies remain inapplicable, thus leaving the CSF as a potential source of biomarkers [ 297 , 298 ]. More recently, as changes in the circulating lipids seem to mirror the dysregulation of their profile in the brain, blood has become a viable alternative to invasive CSF sampling [ 299 , 300 , 301 ]. At the same time, the emergence of cutting-edge techniques, such as peripheral lipidomics, triple quadrupole mass spectrometry, and isobaric tagging methods, have allowed the establishment of lipid signatures potentially associated with AD, even at the prodromal and preclinical stages [ 302 , 303 , 304 ].…”

“…In this respect, while diminished plasma ApoE was reported to predict AD development, ApoA1, ApoH, and ApoJ were found altered in MCI subjects compared to healthy controls [ 301 , 311 ]. Finally, serum 24-hydroxycholesterol, a marker of cholesterol metabolism in the brain [ 330 ], is decreased in AD compared to controls, with its plasma esters being lower in MCI individuals progressing towards AD than in non-progressing individuals [ 299 , 300 ]. However, similar findings have also been described in the context of PD, thus questioning the specificity of this biomarker [ 331 ].…”

The Controversial Role of 24-S-Hydroxycholesterol in Alzheimer’s Disease

“…This trend is also suggested by the work of Papassotiropoulos and collaborators, where, after an initial increase in the earlier phases, reduction of the plasma 24-OHC/cholesterol was associated with severity of AD [ 75 ]. Lower levels of 24-OHC were detected in the serum of patients with greater AD severity associated with increased agitation, bringing out a decrease in 24-OHC levels in the advanced stages of the disease compared to controls [ 76 , 77 ]. A negative correlation between plasma 24-OHC levels and AD severity was found in another investigation, although in this case 24-OHC levels were higher in AD patients than in healthy controls [ 78 ].…”

Increased Plasma Level of 24S-Hydroxycholesterol and Polymorphism of CYP46A1 SNP (rs754203) Are Associated With Mild Cognitive Impairment in Patients With Type 2 Diabetes

“…We finally chose the ELISA method because its sensitivity and accuracy are slightly inferior to other methods. The literature revealed other studies that used the ELISA method to determine the plasma 24-OHC concentration ( Roy et al, 2019 ). We used double-antibody sandwich ELISA, which has high sensitivity and high specificity, to maximize the reliability of the measurement results.…”