ArticleThe American journal of pathology2009
Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 3 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 3 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Proton Pump Inhibitor Use and Risk of Dementia: An Umbrella Review of Systematic Reviews and Meta-Analyses.Digestive diseases and sciences · 2026Pooled it
- Does folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trials.Frontiers in aging neuroscience · 2022Pooled it
- The Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis.Frontiers in neuroscience · 2021Pooled it
- A randomized, controlled trial to evaluate the efficacy of pyridoxine and ascorbic acid on cognitive function and quality of life in post-menopausal women.Naunyn-Schmiedeberg's archives of pharmacology · 2025Trial
- Cross-Sectional Associations of Total Plasma Homocysteine with Cortical β-Amyloid Independently and as a Function of Omega 3 Polyunsaturated Fatty Acid Status in Older Adults at Risk of Dementia.The journal of nutrition, health & aging · 2017Trial
- Decoding the complex nexus: the mechanistic interplay of hyperhomocysteinemia in brain aging and neurological disorders.Biogerontology · 2026Review
- Insights into proton transfer dynamics in histidine tautomers of amyloid-β (1-40).Communications chemistry · 2025Article
- Association and interaction of blood homocysteine and p-tau217 levels with temporal cortical thinning and cognitive impairment in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review.International journal of molecular sciences · 2025Review
- Say hello to my little friend… micronutraceuticals in neuroenergetics, neuronal health, and neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Article
- Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an mRedox biology · 2024Article
- Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms.International journal of molecular sciences · 2024Review
- Impact of common ALDH2 inactivating mutation and alcohol consumption on Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Epigallocatechin-3-gallate Enhances Cognitive and Memory Performance and Protects Against Brain Injury in Methionine-induced Hyperhomocysteinemia Through Interdependent Molecular Pathways.Neurotoxicity research · 2022Article
- Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells.Cells · 2022Article
- Assessment of Neurodegenerative Changes in Turkeys Fed Diets with Different Proportions of Arginine and Methionine Relative to Lysine.Animals : an open access journal from MDPI · 2022Article
- Mechanistic Link between Vitamin B12 and Alzheimer's Disease.Biomolecules · 2022Review
- 29 mJournal of immunology research · 2022Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperhomocysteinemia and beta-amyloid (Abeta) overproduction are critical etiological and pathological factors in Alzheimer disease, respectively; however, the intrinsic link between them is still missing. Here, we found that Abeta levels increased and amyloid precursor protein (APP) levels simultaneously decreased in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine. Concurrently, both the mRNA and protein levels of presenilin-1, a component of gamma-secretase, were elevated, whereas the expression levels of beta-secretase and presenilin-2 were not altered. We also observed that levels of phosphorylated APP at threonine-668, a crucial site facilitating the amyloidogenic cleavage of APP, increased in rats with hyperhomocysteinemia, although the phosphorylation per se did not increase the binding capacity of pT668-APP to the secretases. The enhanced phosphorylation of APP in these rats was not relevant to either c-Jun N-terminal kinase or cyclin-dependent kinase-5. A prominent spatial memory deficit was detected in rats with hyperhomocysteinemia. Simultaneous supplementation of folate and vitamin-B12 attenuated the hyperhomocysteinemia-induced abnormal processing of APP and improved memory. Our data revealed that hyperhomocysteinemia could increase Abeta production through the enhanced expression of gamma-secretase and APP phosphorylation, causing memory deficits that could be rescued by folate and vitamin-B12 treatment in these rats. It is suggested that hyperhomocysteinemia may serve as an upstream factor for increased Abeta production as seen in patients with Alzheimer disease.
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Registered trials
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 OpenQuestion graph.