Evidence mapPaperPMID 41417174Full record

ArticleMolecular neurobiology2025

Association of MTHFR C677T and A1298C Polymorphisms in Metabolic Alterations, Neuroimaging, and Cognitive Decline in Alzheimer's Disease: Case-Control and Bioinformatics Insights.

Anil Kumar Maurya, Mona Srivastava, Shani Vishwakarma, Ashish Ashish, Nitish Kumar Singh, Abhay Kumar Yadav, Royana Singh

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Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Anil Kumar MauryaDepartment of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Mona SrivastavaDepartment of Psychiatry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Shani VishwakarmaDepartment of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Ashish AshishMultidisciplinary Research Unit, Institute of Medical Sciences, ICMR DHR, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Nitish Kumar SinghMultidisciplinary Research Unit, Institute of Medical Sciences, ICMR DHR, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Abhay Kumar YadavDepartment of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
Royana SinghDepartment of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India. royanasingh@bhu.ac.in.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder influenced by genetic, metabolic, and lifestyle factors. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, notably C677T and A1298C, may increase AD susceptibility through disruptions in one-carbon metabolism and homocysteine accumulation. This study examined the association of MTHFR C677T and A1298C variants with metabolic alterations, cognitive decline, and AD risk. A case-control study was conducted with 120 AD patients and 120 cognitively healthy controls. Cognitive function was assessed using the Hindi Mini-Mental State Examination (HMMSE) and Hindi Mattis Dementia Rating Scale (HMDRS). MRI evaluated white matter hyperintensities and cortical atrophy. Biochemical markers, including homocysteine, folate, and vitamin B12, were measured. Genotyping was performed via TaqMan SNP assays. Functional enrichment and protein-protein interaction analyses were conducted to investigate molecular mechanisms. AD cases demonstrated elevated homocysteine and blood glucose, reduced folate, and impaired cognition. Both MTHFR C677T and A1298C polymorphisms were significantly associated with AD risk under dominant and over-dominant models (ORs 3.41-4.09). Risk-allele carriers exhibited pronounced metabolic alterations. Bioinformatics analyses revealed disruption in one-carbon metabolism, oxidative stress defense, and vascular pathways, with indirect interactions between MTHFR and key AD genes (APP, PSEN1/2, MAPT, APOE, CLU, PICALM, SORL1). MTHFR C677T and A1298C variants contribute to AD susceptibility through metabolic and vascular mechanisms that exacerbate cognitive decline. Integrating genetic, biochemical, and cognitive assessments highlights potential targets for early prevention and therapeutic interventions.

Indexed as

Alzheimer DiseaseCognitive DysfunctionComputational BiologyGenetic Association StudiesGenetic Predisposition to DiseaseMethylenetetrahydrofolate Reductase (NADPH2)NeuroimagingPolymorphism, Single NucleotideAgedCase-Control StudiesFemaleFolic AcidHomocysteineHumansMaleFolic AcidHomocysteineMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanA1298CAlzheimer’s diseaseC677THomocysteineMTHFROne-carbon metabolism

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.