PMID- 20519634
OWN - NLM
STAT- MEDLINE
DCOM- 20101101
LR  - 20211020
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 24
IP  - 10
DP  - 2010 Oct
TI  - Normalization of hyperhomocysteinemia improves cognitive deficits and ameliorates 
      brain amyloidosis of a transgenic mouse model of Alzheimer's disease.
PG  - 3895-902
LID - 10.1096/fj.10-161828 [doi]
AB  - Hyperhomocysteine (HHcy) is a risk factor for developing Alzheimer's disease 
      (AD). Previously, we showed that diet-induced HHcy accelerated the AD-like 
      phenotype of a transgenic mouse model, i.e., Tg2576. In the present work, we 
      tested whether an HHcy-lowering strategy in this model would be beneficial. 
      Tg2576 mice received methionine-rich or regular chow diet for 5 mo. Next, while 
      the chow control group was kept on the same regimen, the other mice were 
      randomized into two groups: one was kept on the methionine-rich diet (Met On), 
      the other switched to chow (Met Off). Compared with controls, 5 mo on the 
      methionine-rich diet resulted in HHcy (plasma Hcy level, treated: 12.7+/-1.2 muM vs. 
      control: 3.1+/-0.4 muM) and significant behavioral impairments (% freezing, treated: 
      2.4+/-1.4% vs. control: 19.9+/-6.9%). At the end of the study, while the Met On group 
      kept Hcy level elevated, the Met Off group had these values indistinguishable 
      from the controls. The reduction in Hcy levels resulted in a significant 
      improvement of the fear-conditioning performance, and an amelioration of the 
      brain amyloidosis. Our results demonstrate that lowering HHcy in a transgenic 
      AD-mouse model is beneficial since it significantly improves behavior deficits 
      and brain amyloidosis. Our findings provide new biological insights for future 
      clinical trials aimed at lowering this modifiable risk factor in human AD.
FAU - Zhuo, Jia-Min
AU  - Zhuo JM
AD  - Department of Pharmacology, Temple University School of Medicine, Philadelphia, 
      Pennsylvania, 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
DEP - 20100602
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
SB  - IM
MH  - Amyloidosis/*prevention & control
MH  - Animals
MH  - Cognition Disorders/*metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Hyperhomocysteinemia/*metabolism
MH  - Mice
MH  - Mice, Transgenic
PMC - PMC2996912
EDAT- 2010/06/04 06:00
MHDA- 2010/11/03 06:00
PMCR- 2011/10/01
CRDT- 2010/06/04 06:00
PHST- 2010/06/04 06:00 [entrez]
PHST- 2010/06/04 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - fj.10-161828 [pii]
AID - 10-161828 [pii]
AID - 10.1096/fj.10-161828 [doi]
PST - ppublish
SO  - FASEB J. 2010 Oct;24(10):3895-902. doi: 10.1096/fj.10-161828. Epub 2010 Jun 2.