Homocysteine and holotranscobalamin and the risk of Alzheimer disease

Hooshmand, Babak; Solomon, Alina; Kåreholt, Ingemar; Leiviskä, Jaana; Rusanen, Minna; Winblad, Bengt; Laatikainen, Tiina; Kivipelto, Miia

doi:10.1212/wnl.0b013e3181f88162

Cited by 110 publications

(71 citation statements)

References 42 publications

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“…This subsequently produces of S-adenosylmethionine (SAM), which plays a role in neurotransmitter synthesis and lipid metabolism [1]. Folate deficiency results in elevated levels of plasma homocysteine, which have been associated with cardiovascular disease [2], neurodegeneration [3], impaired cognitive function [4,5], the development of Alzheimer's disease (AD) [6][7][8], and vascular dementia [9][10][11]. However, the neurodegeneration link remains controversial, since other studies have shown no association [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji

Farr

Lips

et al. 2015

Behavioural Brain Research

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(2015) Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. Behavioural Brain Research, 283 . pp. 215-226. ISSN 1872-7549 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/32983/9/UNG_FADD_20140826_manuscript_final.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. ABSTRACTDietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders.Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfusion in an animal model. Ung+/+ and Ung−/− mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung−/− FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung+/+ FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung−/− hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion o...

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Section: Introductionmentioning

confidence: 99%

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji

Farr

Lips

et al. 2015

Behavioural Brain Research

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“…From the therapeutic perspective,methycobalamin rather than cyanocobalamin, may be preferable in elderly patients with impaired renal function. A very recent study of the AD risk showed that both total Hcy and holoTranscobalamin (TC) may be involved in normal aging and AD : both plasma biomarkers are correlated with MRI imaging indices of brain volume loss and hyper-density white matter [44,43]. The odds ratios (ORs) (95% confidence interval [CI]) for AD were 1.16 (1.04-1.31) per increase of 1 μmol/L of tHcy at baseline and 0.980 (0.965-0.995) for each increase of 1 pmol/L baseline holoTC.The putative Hcy-AD may be mediated in part by the serum holoTC.…”

Section: Discussionmentioning

confidence: 99%

Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

Chiu¹,

Khan²,

Badmaev³

et al. 2017

J Syst Integr Neurosci

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Introduction: There is mounting evidence to suggest that hyper-homocysteinemia (eHct) correlates with cognitive decline severity and cortical atrophy in AD. Hydrogen Sulfide (H 2 S) exerts neuroprotection through regulating Homocysteine (eHcy) signaling. Elemental sulfur can mediate H 2 S neuroprotection through the trans-sulfuration pathway and correct the the dysregulation of H 2 S /Hct signaling in AD. Sublimed Sulfur, formulated as SULMEDOL and approved for the treatment of lactose intolerance, activates gut beta-galactosidase (GALAC). We repurpose Sulmedol from lactose intolerance to likely CNS effect, since gut GALAC cross-talks with senescence-related GALAC expression in the brain. In view of the known regulatory function of GALAC in CNS endosomal-lysosomal autophagy system , we propose that SULMEDOL may rescue aberrant autophagy in AD.

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“…These findings indicate that the replenishment To date, an agreement on the correlation between HHcy and cognitive function has not been reached. Some scholars believe that HHcy serves as an independent risk factor of cognitive disorder or a decrease in cognitive function (16,17), whereas some hold that HHcy has nothing to do with cognitive function (19). To the formers two channels through which HHcy leads to cognitive disorder are believed to exist.…”

Section: Discussionmentioning

confidence: 99%

Intervention Effect of Folic Acid and Vitamin B12 on Vascular Cognitive Impairment Complicated With Hyperhomocysteinemia / Efekat Intervencije Folnom Kiselinom I Vitaminom B12 Na Vaskularni Kognitivni Poremećaj Komplikovan Hiperhomocisteinemijom

Jiang¹,

Cheng-yun²,

Yao³

et al. 2013

Journal of Medical Biochemistry

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SummaryBackground: Hyperhomocysteinemia (HHcy) may be correlated with cognitive function. Although intervention with folic acid and VitB 12 can decrease the homocysteine (Hcy) level, its effect on cognitive function remains uncertain. This prospective study aimed to explore the effects of folic acid and VitB 12 on the Hcy level and cognitive function in patients with vascular cognitive impairment-no dementia (VCIND) complicated with HHcy. Methods: A total of 120 patients with VCIND complicated by HHcy were randomly selected. They were divided into intervention and control groups. The intervention group was given 5 mg of folic acid per day and 500 mg of VitB 12 thrice per day apart from conventional therapy. Folic acid, VitB 12 , and Hcy were determined and Montreal cognitive assessment (MoCA) and event-related potential P300 determination were performed before and after treatment. Results: Before treatment, no significant differences in the folic acid, VitB 12 , Hcy, MoCA, and P300 parameters were observed between the groups. After treatment, the folic acid and VitB 12 levels increased and the Hcy level decreased in the intervention group compared with that before treatment and in the control group. At 24 weeks, the MoCA score and P300 outcomes in the intervention group improved compared with those before treatment and in the control group. Conclusions: Folic acid and VitB 12 effectively decrease the Hcy level in VCIND patients and improve their cognitive functions.

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Homocysteine and holotranscobalamin and the risk of Alzheimer disease

Abstract: This study suggests that both tHcy and holoTC may be involved in the development of AD. The tHcy-AD link may be partly explained by serum holoTC. The role of holoTC in AD should be further investigated.

Cited by 110 publications

References 42 publications

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

Intervention Effect of Folic Acid and Vitamin B12 on Vascular Cognitive Impairment Complicated With Hyperhomocysteinemia / Efekat Intervencije Folnom Kiselinom I Vitaminom B12 Na Vaskularni Kognitivni Poremećaj Komplikovan Hiperhomocisteinemijom

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