Vitamin E and Enzymatic/Oxidative Stress-Driven Oxysterols in Amnestic Mild Cognitive Impairment Subtypes and Alzheimer's Disease

Abstract

Oxidative stress, which contributes to neuronal damage, is thought to be a pathophysiological mechanism of Alzheimer's disease (AD). Markers of oxidative stress may appear early in the preclinical, mild cognitive impairment (MCI) phase of AD. We investigated the interaction among enzymatic-derived oxysterols (24S-hydroxycholesterol and 27-hydroxycholesterol), markers of oxidative stress, including free radical-related oxysterols (7β-hydroxycholesterol and 7-ketocholesterol), and vitamin E in AD patients and two amnestic MCI subtypes, amnestic single-domain MCI (a-MCI) subjects, and multi-domain MCI (md-MCI) subjects, compared to healthy control subjects (HC). The study included 37 patients with AD, 24 with a-MCI, 29 with md-MCI, and 24 HC. Plasma assessments were made using isotope dilution-mass spectrometry. Although we found no significant change in free radical-or enzymatic-derived oxysterol concentrations in AD or MCI patients, vitamin E levels corrected for cholesterol were reduced in AD patients compared to HC. Results suggest that AD patients have upregulated cerebral oxidative stress or a nutritional deficit of vitamin E. The oxysterols investigated here are not useful markers for diagnosing AD or MCI.

Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

“…However, it has been observed that, in glial cells, and especially around senile plaques, there is an ectopic induction of CYP46A1, leading to some 24-OH production, but without compensating for the decrease of that oxysterol (Bogdanovic et al, 2001; Brown et al, 2004). Another study, however, has found that plasma levels of 24-OH and 27-OH in AD patients are not significantly different from control values (Iuliano et al, 2010). A small fraction of total 24-OH excretion occurs via the CSF, and the 24-OH concentration is increased in the CSF of AD patients, probably reflecting neuronal damage and loss rather then metabolically active neuronal cells (Schönknecht et al, 2002; Leoni et al, 2004).…”

Inverse Association Between Serum Uric Acid Levels and Alzheimer’s Disease Risk

“…Of the remaining 35 studies, 6 studies were excluded for irrelevant outcomes and 5 studies were excluded for no usable data. Thus, 24 studies were finally included into the meta-analysis [14][15][16][17][18][19][20][21][22][23][24][28][29][30][31][32][33][34][35][36][37][38][39][40]. Among those 24 studies, 21 were case-control studies comparing serum uric acid levels in Alzheimer's disease patients with healthy controls [14-24, 28-32, 36-40] and 3 studies were cohort studies assessing risk of Alzheimer's disease in individuals with various categories of serum uric acid levels [33][34][35].…”

“…Among those 24 studies, 21 were case-control studies comparing serum uric acid levels in Alzheimer's disease patients with healthy controls [14-24, 28-32, 36-40] and 3 studies were cohort studies assessing risk of Alzheimer's disease in individuals with various categories of serum uric acid levels [33][34][35]. Among those 24 studies, 19 studies were published in English [14][15][16][17][18][19][20][21][22][23][24][28][29][30][31][32][33][34][35] while the other 5 studies were published in Chinese [36][37][38][39][40]. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease [14-24, 28-32, 36-40].…”

“…Considering the protective effect of uric acid on nerves, the association between Alzheimer's disease and uric acid levels had gained great interest in recent years [14][15][16][17][18][19][20][21][22][23][24]. There were a number of studies performed to assess the association between Alzheimer's disease and uric acid levels, but no definite evidence was available [14][15][16][17][18][19][20][21][22][23][24]. We thus performed a systematic review and meta-analysis of relevant studies to comprehensively estimate the association.…”

Relationship Between Cholesterol Metabolism, Apoe and Brain Volumes In Alzheimer‘s Disease

“…In only one study was the plasma concentrations of 24-OHC found to be significantly increased in patients with AD or vascular dementia, which would be in agreement with the hypothesis that neuronal damage could be associated with a higher turnover of neuronal membranes, which provides higher levels of cholesterol to be converted into 24-OHC [125]. Another study reports that plasma levels of 24-OHC in AD patients were not significantly different from those in control subjects [126]. However, more consistent findings reported that a reduction of plasma 24-OHC was correlated with the severity of dementia or the degree of brain atrophy [72,78].…”