A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer’s disease

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-l-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia—a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B12 (methylcobalamin), vitamin B9 (folic acid), vitamin B6 (pyridoxine), and SAM to patients in early stages of LOAD.

Download Full-text

Precision Medicine for Alzheimer’s Disease Prevention

Healthcare ◽

10.3390/healthcare6030082 ◽

2018 ◽

Vol 6 (3) ◽

pp. 82 ◽

Cited By ~ 5

Author(s):

Cara Berkowitz ◽

Lisa Mosconi ◽

Olivia Scheyer ◽

Aneela Rahman ◽

Hollie Hristov ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Precision Medicine ◽

Methylenetetrahydrofolate Reductase ◽

Late Onset ◽

Individual Variability ◽

Prevention Strategy ◽

Response To Treatment ◽

Ad Prevention

Precision medicine is an approach to medical treatment and prevention that takes into account individual variability in genes, environment, and lifestyle and allows for personalization that is based on factors that may affect the response to treatment. Several genetic and epigenetic risk factors have been shown to increase susceptibility to late-onset Alzheimer’s disease (AD). As such, it may be beneficial to integrate genetic risk factors into the AD prevention approach, which in the past has primarily been focused on universal risk-reduction strategies for the general population rather than individualized interventions in a targeted fashion. This review discusses examples of a “one-size-fits-all” versus clinical precision medicine AD prevention strategy, in which the precision medicine approach considers two genes that can be commercially sequenced for polymorphisms associated with AD, apolipoprotein E (APOE), and methylenetetrahydrofolate reductase (MTHFR). Comparing these two distinct approaches provides support for a clinical precision medicine prevention strategy, which may ultimately lead to more favorable patient outcomes as the interventions are targeted to address individualized risks.

Download Full-text

The C677T polymorphism of the methylenetetrahydrofolate reductase gene and susceptibility to late-onset Alzheimer’s disease

Open Medicine ◽

10.1515/med-2019-0006 ◽

2019 ◽

Vol 14 (1) ◽

pp. 32-40 ◽

Cited By ~ 3

Author(s):

Jian Yi ◽

Lan Xiao ◽

Sheng-Qiang Zhou ◽

Wen-Jiang Zhang ◽

Bai-Yan Liu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Methylenetetrahydrofolate Reductase ◽

Late Onset ◽

Meta Analysis ◽

Mthfr C677t ◽

Case Control ◽

Cochrane Library ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism

AbstractFolate metabolism makes a crucial contribution towards late-onset Alzheimer’s disease (LOAD). Moreover, methylenetetrahydrofolate reductase (MTHFR) constitutes the primary enzyme of the folate pathway. We hypothesize that there is an association of C677T polymorphism in the MTHFR gene with the susceptibility to LOAD. Previous published research has investigated the link between the MTHFR C677T polymorphisms and LOAD susceptibility; nevertheless, the findings have continued to be not only controversial, but also indecisive. Accordingly, we carried out the present meta-analysis for the assessment of the potential link that exists between the MTHFR C677T polymorphism and the susceptibility to LOAD. Furthermore, we carried out a literature search of the PubMed, EMBASE, Cochrane Library, and WanFang database up to August 10, 2018. The odds ratios (ORs) with the respective 95% confidence interval (95%CI) were put to use for the evaluation of the robustness of the link of the MTHFR C677T polymorphism with the vulnerability to LOAD. All statistical analyses were carried out using STATA 15.0. An aggregate of 14 case-control research works was retrieved, involving 2,467 LOAD patients as well as 2,877 controls. We found that a substantial link exists between C677T polymorphism and LOAD risk in a codominant framework (TC vs. CC: OR=1.22, 95%CI=1.00-1.49, P=0.049). In addition to the stratified analysis based on ethnicity, which suggested that C677T polymorphism was likely linked only to an augmented threat of LOAD in Asians, it did not exist among Caucasians. Furthermore, in the subgroup analysis carried out using APOE ɛ4 status, a substantial increase in the susceptibility to LOAD was detected in APOE ɛ4 carriers as well as non-APOE ɛ4 carriers. In sum, the current meta-analysis revealed that MTHFR C677T polymorphism was associated with susceptibility to LOAD. Further extensive case-control studies are required.

Download Full-text

Methylenetetrahydrofolate reductase C667T polymorphism and susceptibility to late-onset Alzheimer's disease in the Italian population

Minerva Medica ◽

10.23736/s0026-4806.20.06801-9 ◽

2021 ◽

Vol 112 (3) ◽

Author(s):

Marco ZUIN ◽

Carlo CERVELLATI ◽

Alessandro TRENTINI ◽

Loris RONCON ◽

Patrizia GUASTI ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Methylenetetrahydrofolate Reductase ◽

Late Onset ◽

Italian Population

Download Full-text

Familial Patterns of Risk in Very Late-Onset Alzheimer's Disease

PsycEXTRA Dataset ◽

10.1037/e334202004-004 ◽

2003 ◽

Author(s):

J. M. Silverman ◽

C. J. Smith ◽

D. B. Marin ◽

R. C. Mohs ◽

C. B. Propper

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Familial Patterns

Download Full-text

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

Current Protein and Peptide Science ◽

10.2174/1389203721666200921152246 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1164-1173

Author(s):

Siju Ellickal Narayanan ◽

Nikhila Sekhar ◽

Rajalakshmi Ganesan Rajamma ◽

Akash Marathakam ◽

Abdullah Al Mamun ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Precursor Protein ◽

Early Onset ◽

Late Onset ◽

Precursor Protein ◽

Brain Disorder ◽

Amyloid Aβ ◽

T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

Download Full-text