Document Detail


Severe In vivo hyper-homocysteinemia is not associatedwith elevation of amyloid-beta peptides in the Tg2576 mice.
MedLine Citation:
PMID:  20555139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Since hyper-homocysteinemia (HHcy) was recognized as a risk factor for Alzheimer's disease (AD), many studies tried to induce HHcy in animal models to investigate its effect on amyloid-beta protein precursor (AbetaPP) metabolism. Previous reports found that HHcy induced in AD transgenic mouse models, by either feedina a methionine-enriched diet or vitamin Bs deficient diet, is associated with elevation of amyloid-beta (Abeta) levels. However, there is no data available on the effect of dietary intervention which combines both excessive methionine and low levels of vitamin Bs on amyloidogenesis in any of these models. In the current study, we investigated the effect of a combination diet, which was both enriched in methionine and deficient in folate, vitamin B6 and B12, in an AD mouse model, the Tg2576. We found that 7 months treatment of this diet induced severe HHcy in these mice with plasma homocysteine level higher than 150 microM. However, no difference was detected in brain Abeta levels or deposition between the diet-treated and control group. As shown by western blot, severe HHcy did not alter the steady state levels of proteins involved in AbetaPP metabolism, either. These results demonstrate that this combination diet-induced severe HHcy does not influence amyloidogenesis in vivo.
Authors:
Jia-Min Zhuo; Domenico Praticò
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  21     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-11-02     Revised Date:  2011-02-23    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  133-40     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / etiology*,  genetics,  metabolism*,  pathology
Amyloid beta-Peptides / metabolism*
Amyloid beta-Protein Precursor / genetics
Animals
Cerebral Cortex / metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay / methods
Gene Expression Regulation / genetics
Hippocampus / metabolism
Humans
Hyperhomocysteinemia / chemically induced,  complications*,  pathology
Methionine / administration & dosage
Mice
Mice, Transgenic
Peptide Fragments / metabolism*
Random Allocation
Vitamin B 12 / administration & dosage
Grant Support
ID/Acronym/Agency:
AG-22512/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Peptide Fragments; 0/amyloid beta-protein (1-40); 0/amyloid beta-protein (1-42); 63-68-3/Methionine; 68-19-9/Vitamin B 12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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