Cyp46 Polymorphisms in Alzheimer’s Disease: A Review

Garcia, Anália Nusya; Muniz, Maria Tereza Cartaxo; Silva, Hugo Rafael Souza e; Silva, Helker Albuquerque da; Athayde-Junior, Luiz

doi:10.1007/s12031-009-9227-2

Cited by 31 publications

(24 citation statements)

References 34 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, CYP46A1 is preferentially expressed in degenerating neurites surrounding senile plaque in brains of AD patients (Brown and others 2004). Furthermore, association of CYP46A1 polymorphisms with risk of AD and elevated Aβ load has been reported (Garcia and others 2009; Papassotiropoulos and others 2003). The abnormal induction and distribution of CYP46A1 in brains of AD patients suggest that 24S-HC, in addition to being an indicator for AD diagnosis, may be more directly involved in AD pathogenesis.…”

Section: S-hc and Alzheimer’s Diseasementioning

confidence: 99%

24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival

et al. 2015

View full text Add to dashboard Cite

The major cholesterol metabolite in brain, 24S-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on NMDA receptor (NMDAR) function. This could have implications for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and downregulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.

show abstract

Section: S-hc and Alzheimer’s Diseasementioning

confidence: 99%

24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Genetic variation in 24-hydroxylase enzyme not only alters 24-OHC production but it is associated with an increased load of Aβ [8] and AD (see review of CYP46A1 and AD by Garcia et al [9]). 24-hydroxylase metabolizes cholesterol with the addition of a hydroxyl group at the 24-position.…”

Section: Cholesterol Synthesis and Metabolism In The Brainmentioning

confidence: 99%

Brain Cholesterol Metabolism, Oxysterols, and Dementia

Hughes

Rosano

Evans

et al. 2013

JAD

View full text Add to dashboard Cite

Cholesterol metabolism is implicated in the etiology of Alzheimer’s disease (AD) and amyloid production in the brain. While brain cholesterol cannot be measured directly in vivo, the oxysterol, 24S-hydroxycholesterol (24-OHC), is the predominant metabolite of brain cholesterol and can be measured in the blood. The aim of this review is to evaluate plasma 24-OHC as a potential biomarker of AD risk and discuss factors related to its levels in the brain and blood. This systematic review examines studies published between 1950 and June 2012 that examined the relationship between plasma 24-OHC, cognition, brain structure, and dementia using the following key words (“24S-hydroxycholesterol” or “24-hydroxycholesterol”) and (“Brain” or “Cognitive”). We found a total of 28 studies of plasma 24-OHC and neurodegenerative disease, including a subset of 12 that used dementia as a clinical endpoint. These studies vary in the direction of the observed associations. Results suggest plasma 24-OHC may be higher in the early stages of cognitive impairment and lower in more advanced stages of AD when compared to cognitively normal controls. Measures of 24-OHC in the blood may be an important potential marker for cholesterol metabolism in the brain and risk of AD. Further studies of plasma 24-OHC and dementia must account for the stage of disease, establish the temporal trends in oxysterol concentrations, and employ neuroimaging modalities to assess the structural and metabolic changes occurring in the brain prior to the onset of cognitive impairment.

show abstract

“…The TT genotype in intron 2 of CYP46A1 , designated as the rs754203 SNP, has been identified as a risk factor for Alzheimer disease,[678] and more recently, for POAG. [18] CYP46A1 and its metabolic product 24S-hydroxycholesterol are specific for the neural retina, and especially for retinal ganglion cells.…”

Section: Discussionmentioning

confidence: 99%

“…A single-nucleotide polymorphism (SNP) in the CYP46A1 gene, designated as rs754203 and associated with Alzheimer disease, was evaluated as a genetic risk factor for primary open-angle glaucoma (POAG) as well as plasma 24S-hydroxycholesterol levels. [7] Cholesterol-24S-hydroxylase was initially identified as a cholesterol-metabolizing enzyme in the brain. Accumulating evidence suggests that cholesterol is a risk factor for Alzheimer's disease;[8910] CYP46A1 has also been detected in rodent and bovine retinal ganglion cells, indicating a physiologic role in the cholesterol metabolism of the mammalian retina.…”

Section: Introductionmentioning

confidence: 99%

Association of angiotensin-converting enzyme, CYP46A1 genes polymorphism with senile cataract

et al. 2017

View full text Add to dashboard Cite

Background:Senile cataract is the most common type of cataract characterized by gradual progressive thickening of the lens of the eye. Previously, many studies investigated the association between genetic polymorphism and senile cataract. Angiotensin-converting enzyme (ACE) I/D polymorphism is the potential risk factor for many eye-related diseases such as retinopathy and glaucoma. CYP46A1 enzyme converts cholesterol to 24S-hydroxycholesterol; human lens' membranes contain the highest cholesterol content. Defects in enzymes of cholesterol metabolism can be associated with cataracts. Hence, the present study was carried out to investigate the association of ACE and CYP46A1 genes polymorphism with senile cataract cases and controls.Materials and Methods:ACE (rs 4646994) and CYP46A1 (rs 754203) genes polymorphism in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism.Results:This study included 103 senile cataract cases (55 were males and 48 were females) and 102 controls (53 were males and 49 were females). Mean age of cases in this study was 52.02 ± 12.11 years while in control group 53.74 ± 11.87 years. Frequencies of ACE ID, DD, and II genotypes in senile cataract cases were 64.07%, 4.85%, and 31.06% and controls were 61.76%, 26.47%, and 11.76%, respectively. The CYP46A1 gene CT, CC, and TT genotype frequencies were 48.54%, 8.73%, and 42.71% in senile cataract cases and 28.43%, 3.92%, and 67.64% in healthy controls, respectively. ACE DD and II genotypes (P < 0.001,P = 0.0008) and CYP46A1 CT and TT genotypes (P = 0.003,P = 0.0003) were significantly associated with senile cataract cases compared to the controls.Conclusion:Findings of this study suggest that ACE and CYP46A1 genes polymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genes polymorphism as a marker of susceptibility to senile cataract needs further validation in studies involving larger number of patients from different regions.

show abstract

Cyp46 Polymorphisms in Alzheimer’s Disease: A Review

Cited by 31 publications

References 34 publications

24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival

24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival

Brain Cholesterol Metabolism, Oxysterols, and Dementia

Association of angiotensin-converting enzyme, CYP46A1 genes polymorphism with senile cataract

Contact Info

Product

Resources

About