The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice

Document Type

Article

Publication Date

12-1-2022

Publication Title

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Keywords

JMG, Mice, Animals, Humans, Methylenetetrahydrofolate Reductase (NADPH2), Positron Emission Tomography Computed Tomography, Mice, Inbred C57BL, Folic Acid, Genetic Predisposition to Disease, Genotype

JAX Source

J Cereb Blood Flow Metab. 2022;42(12):2333-50

Volume

42

Issue

12

First Page

2333

Last Page

2350

ISSN

1559-7016

PMID

36050860

DOI

https://doi.org/10.1177/0271678x221122644

Grant

We would like to acknowledge funding support from the Diana Davis Spencer Foundation (Howell), BrightFocus Foundation (grant no. A2020677F) (Reagan), the Canadian Institutes of Health Research (grant no. PJT173521) (Rozen), National Institute on Aging (grant no.U54AG054345) (MODEL-AD). Collection and sharing of human data used in this study was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01AG024904) and DODADNI (Department of Defense award number W81XWH-12-2- 0012).

Abstract

Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimer's disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in

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