24S-hydroxycholesterol in plasma: A marker of cholesterol turnover in neurodegenerative diseases

Accumulation of 24S-hydroxycholesterol in neuronal SK-N-BE cells treated with hexacosanoic acid (C26:0): Argument in favor of 24S-hydroxycholesterol as a potential biomarker of neurolipotoxicity

“…Nevertheless, our data support that increased level of 24S-OH (only produced by neurons [20]) might reflect neuronal dysfunctions associated with neurotoxic effects in some neurodegenerative diseases [21]. Therefore, our present data obtained in vitro support that the measurement of 24S-OHC, which could constitute a potential biomarker in various neurological diseases [6,22], might have some interests to assess neuronal cytotoxicity, especially lipotoxicity, and to evaluate the efficiency of treatments capable to preserve and/or counteract neuronal damages (Fig. 2).…”

“…As previous studies reported that 24S-hydroxycholesterol (24S-OHC) is frequently enhanced in the plasma of patients with various neurodegenerative diseases [6], it is tempting to speculate that an enhanced level of 24S-OHC could be increased in certain forms of neurotoxicity. To evaluate this hypothesis, we asked whether hexacosanoic acid (C26:0), found at increased levels in the plasma and tissues of patients with leukodystrophies [7,8], as well as in the brain and plasma of patients with AD [1][2][3], which has been previously shown to induced cell death associated with oxidative stress on various neuronal cell types including SK-N-BE cells [9,10], was able to favor an accumulation of 24S-OHC in these cells.…”

Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory

“…Brain cholesterol metabolism can be indirectly measured in the blood as oxysterols, and a disproportionate ratio between brain and serum cholesterol metabolism has been linked to the development of dementia and other neurodegenerative conditions (Hughes, Rosano, Evans, & Kuller, 2013). This suggests that cholesterol levels, particularly as they interact with brain cholesterol metabolites, may play an important role in maintaining adequate brain and cognitive health (Leoni & Caccia, 2013; Presecki et al, 2011; van den Kommer et al, 2009). Moreover, a recent study found that serum markers of such imbalance are more associated with CVD than AD (Hughes et al, 2012).…”

The role of lipid peroxidation in neurological disorders

“…(42) Consistent with this, Leoni and Cacciam reported reduced levels of 24(S)-OHCh in neurodegenerative diseases, including Alzheimer’s disease (AD), and suggested that the reduction of 24(S)-OHCh was related to the degree of atrophy in the brain. (41) In contrast, slightly increased 24(S)-OHCh levels have been observed in cases of mild cognitive impairment and in patients with AD. (43) …”

“…Furthermore, 24-hydroxylase (CYP46A1), an enzyme found exclusively in the brain and retina, yields 24(S)-hydroxycholesterol [24(S)-OHCh] as a specific product, (40) which has been reported to play an important role in affecting cholesterol metabolism in the brain. (41) Because almost all plasma 24(S)-OHCh seem to generate in brain, plasma levels of 24(S)-OHCh are considered to be reflective of the number of metabolically-active neurons. (42) Consistent with this, Leoni and Cacciam reported reduced levels of 24(S)-OHCh in neurodegenerative diseases, including Alzheimer’s disease (AD), and suggested that the reduction of 24(S)-OHCh was related to the degree of atrophy in the brain.…”