title: Dietary supplementation with S-adenosyl methionine delayed amyloid-β and tau pathology in 3xTg-AD mice.
abstract: 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.
authors: Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, UMass Lowell, Lowell, MA 01821, USA.
authors: Sangmook
authors: S
authors: Lee
authors: Cynthia A
authors: CA
authors: Lemere
authors: Jeffrey L
authors: JL
authors: Frost
authors: Thomas B
authors: TB
authors: Shea
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000178:diet therapy* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D012436:S-Adenosylmethionine / Q000008:administration & dosage*; D024801:Tauopathies / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D016875:tau Proteins / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D012436:S-Adenosylmethionine