Hyperhomocysteinemia Is a Risk Factor for Alzheimer's Disease in an Algerian Population

Nazef, Khaled; Khelil, Malika; Chelouti, Hiba; Kacimi, Ghouti; Bendini, Mohamed; Tazir, Mériem; Belarbi, Soreya; Cherifi, M.; Djerdjouri, Bahia

doi:10.1016/j.arcmed.2014.03.001

Cited by 22 publications

(17 citation statements)

References 28 publications

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“…A significantlyhigher level of Hcy was also found in this present study. A higher level of Hcy was a risk factor of AD [61] and may cause learning and memory deficits by generating reactive oxygen species [62]. CRP involved in the systemic response to inflammation [63], and our results were consistent with an earlier study which found reduced levels of plasma CRP in AD [64].…”

Section: Discussionsupporting

confidence: 91%

Elevation of Peripheral BDNF Promoter Methylation Links to the Risk of Alzheimer's Disease

Chang

Wang

et al. 2014

PLoS ONE

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Brain derived neurotrophic factor (BDNF) has been known to play an important role in various mental disorders or diseases such as Alzheimer's disease (AD). The aim of our study was to assess whether BDNF promoter methylation in peripheral blood was able to predict the risk of AD. A total of 44 AD patients and 62 age- and gender-matched controls were recruited in the current case-control study. Using the bisulphite pyrosequencing technology, we evaluated four CpG sites in the promoter of the BDNF. Our results showed that BDNF methylation was significantly higher in AD cases than in the controls (CpG1: p = 10.021; CpG2: p = 0.002; CpG3: p = 0.007; CpG4: p = 0.005; average methylation: p = 0.004). In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = −0.308, p = 0.042; glucose: r = −0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = −0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = −0.373, p = 0.016; females: r = −0.399, p = 0.021). Our work suggested that peripheral BDNF promoter methylation might be a diagnostic marker of AD risk, although its underlying function remains to be elaborated in the future.

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Section: Discussionsupporting

confidence: 91%

Elevation of Peripheral BDNF Promoter Methylation Links to the Risk of Alzheimer's Disease

Chang

Wang

et al. 2014

PLoS ONE

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“…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].…”

Section: Characteristics Of Included Studiesmentioning

confidence: 98%

“…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].…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

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

Hou

et al. 2015

Mol Neurobiol

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The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95% CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95% CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease.

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“…Zhuo et al [44] described in their review the clinical studies that cover both the retrospective and prospective studies till 2011, showing elevation of Hcy with the progression of AD. The data summarized in table 1 describe the clinical studies carried out from 2012 to 2014 [45][46][47][48][49][50][51][52] (table 1).…”

Section: Elevated Level Of Hcy and Alzheimer's Diseasementioning

confidence: 99%

Hyperhomocysteinemia: Impact on Neurodegenerative Diseases

Sharma

Tiwari

2015

Basic Clin Pharmacol Toxicol

103

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Neurodegenerative diseases are the diseases of the central nervous system with various aetiology and symptoms. Dementia, Alzheimer's disease (AD), Parkinson's disease (PD) and autism are some examples of neurodegenerative diseases. Hyperhomocysteinemia (Hhcy) is considered to be an independent risk factor for numerous pathological conditions under neurodegenerative diseases. Along with genetic factors that are the prime cause of homocysteine (Hcy) imbalance, the nutritional and hormonal factors are also contributing to high Hcy levels in the body. Numerous clinical and epidemiological data confirm the direct correlation of Hcy levels in the body and generation of different types of central nervous system disorders, cardiovascular diseases, cancer and others. Till now, it is difficult to say whether homocysteine is the cause of the disease or whether it is one of the impacts of the diseases. However, Hhcy is a surrogate marker of vitamin B deficiency and is a neurotoxic agent. This Mini Review will give an overview of how far research has gone into understanding the homocysteine imbalance with prognostic, causative and preventive measures in treating neurodegenerative diseases.Over the last 45 years, the term 'hyperhomocysteinemia (Hhcy)' makes its own space in the medical dictionary. It was initiated with the research of McCully in 1969 who suggested that metabolic effects of increased concentration of homocysteine (Hcy) or a derivative of Hcy could be a cause of arterial damage in both homocystinuria and defects in the cblC gene in vitamin B12 [1]. After long years of research, scientists have arrived at the point that 4.4-10.8 lmol of Hcy per litre of blood is the normal range and any range higher than this will be considered a risk factor for human health [2]. A study by Lindenbaum showed that a high level of Hcy is not just the cause of arterial damage but also a marker of vitamin B12 deficiency in patients with neuropsychiatric disorder [3,4]. Till now, it is not very clear whether the elevated level of Hcy in the body causes neurodegenerative diseases or whether the level of Hcy elevated due to initiation and progression of neurodegenerative diseases. In this Mini Review, we will try to focus on the research outcome for both of the aspects till now. Metabolism of HomocysteineMethionine is a proteinogenic amino acid entering the body through the dietary proteins and is used to synthesize other important proteins in the body. It also acts as a precursor of Hcy. Both methionine and Hcy work in combination to maintain the levels of several proteins in the body. To fulfill the need of Hcy in the body, methionine is converted to S-adenosyl methionine (SAM) through activation by ATP. SAM acts as a major methyl donor in the cell, and after donating the methyl group, it is converted to S-adenosyl homocysteine (SAH), which is hydrolysed to Hcy [5]. The two main pathways, remethylation and trans-sulphuration, balance the level of methionine and Hcy in the body ( fig. 1). Remethylation is the process of adju...

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Hyperhomocysteinemia Is a Risk Factor for Alzheimer's Disease in an Algerian Population

Cited by 22 publications

References 28 publications

Elevation of Peripheral BDNF Promoter Methylation Links to the Risk of Alzheimer's Disease

Elevation of Peripheral BDNF Promoter Methylation Links to the Risk of Alzheimer's Disease

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

Hyperhomocysteinemia: Impact on Neurodegenerative Diseases

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