PMID- 20555139 OWN - NLM STAT- MEDLINE DCOM- 20101102 LR - 20211020 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 21 IP - 1 DP - 2010 TI - Severe In vivo hyper-homocysteinemia is not associatedwith elevation of amyloid-beta peptides in the Tg2576 mice. PG - 133-40 LID - 10.3233/JAD-2010-100171 [doi] AB - 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. FAU - Zhuo, Jia-Min AU - Zhuo JM AD - Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. FAU - Pratico, Domenico AU - Pratico D LA - eng GR - R01 AG022512/AG/NIA NIH HHS/United States GR - AG-22512/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (1-40)) RN - 0 (amyloid beta-protein (1-42)) RN - AE28F7PNPL (Methionine) RN - P6YC3EG204 (Vitamin B 12) SB - IM MH - Alzheimer Disease/*etiology/genetics/*metabolism/pathology MH - Amyloid beta-Peptides/*metabolism MH - Amyloid beta-Protein Precursor/genetics MH - Animals MH - Cerebral Cortex/metabolism MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay/methods MH - Gene Expression Regulation/genetics MH - Hippocampus/metabolism MH - Humans MH - Hyperhomocysteinemia/chemically induced/*complications/pathology MH - Methionine/administration & dosage MH - Mice MH - Mice, Transgenic MH - Peptide Fragments/*metabolism MH - Random Allocation MH - Vitamin B 12/administration & dosage PMC - PMC3880572 MID - NIHMS540543 EDAT- 2010/06/18 06:00 MHDA- 2010/11/03 06:00 PMCR- 2014/01/04 CRDT- 2010/06/18 06:00 PHST- 2010/06/18 06:00 [entrez] PHST- 2010/06/18 06:00 [pubmed] PHST- 2010/11/03 06:00 [medline] PHST- 2014/01/04 00:00 [pmc-release] AID - VH850J00760631W5 [pii] AID - 10.3233/JAD-2010-100171 [doi] PST - ppublish SO - J Alzheimers Dis. 2010;21(1):133-40. doi: 10.3233/JAD-2010-100171.