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Dietary Supplementation with S-Adenosyl Methionine Delayed Amyloid-β and Tau Pathology in 3xTg-AD Mice.
MedLine Citation:
PMID:  22045486     Owner:  NLM     Status:  Publisher    
S-adenosyl methionine (SAM) contributes to multiple pathways in neuronal homeostasis, several of which are compromised in age-related neurodegeneration and Alzheimer's disease. Dietary supplementation of transgenic mice with SAM maintained acetylcholine levels, cognitive performance, oxidative buffering capacity, and phosphatase activity, and reduced aggression, calcium influx, endogenous PS-1 expression, γ-secretase activity, and levels of amyloid-β (Aβ) and phospho-tau. Herein, we examined whether or not SAM could delay neuropathology in 3xTg-AD mice, which harbor mutant genes for human AβPP, PS-1 and tau. Mice received a standard AIN-76 diet with or without SAM (100 mg/kg diet) for 1 month commencing at 10 months of age or for 3 months commencing at 12.5 months of age; mice were sacrificed and examined for Aβ and tau neuropathology at 11 and 15.5 months of age, respectively. SAM supplementation reduced hippocampal intracellular AβPP/Aβ and phospho-tau immunoreactivity to a similar extent at both sampling intervals. Supplementation reduced the number of extracellular Aβ deposits by 80% (p < 0.01) at 11 months of age after 1 month of treatment but only by 24% (p < 0.34) at 15.5 months of age after 3 months of treatment. As anticipated, neurofibrillary tangles were not observed in mice at these young ages; however, supplementation reduced levels of phospho-tau and caspase-cleaved tau within Sarkosyl-insoluble preparations in mice at 15.5 months of age. These limited analyses indicate that SAM can modulate the time course of AD neuropathology, and support further long-term analyses.
Sangmook Lee; Cynthia A Lemere; Jeffrey L Frost; Thomas B Shea
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-1
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  -     ISSN:  1875-8908     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, UMass Lowell, Lowell, MA, USA.
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