Table 4.

Diet-induced HHcy studies in AD transgenic mouse models

Mouse strain	Diet	Starting age	Duration	Hcy level	Effect	study
APP695 Line C3-3	No folate 4.5g/kg D,L-homocysteine	7 months old	3 months	Increased from 3 µm to 27 µm	Hippocampus neuronal death No change in Aβ levels	Kruman, Kumaravel et al. 2002 69
Tg2576	No folate No methionine 4.5g/kg D,L-homocysteine	16–18 months old	6 months	Increased from 100 µm to 200 µm	Impaired water maze performance No change in Thioflavin-S-staining of amyloid aggregate	Bernardo McCord et al. 2007 106
	Methionine 7.7g/kg	8 months old	7 months	Increased from 6 µm to 35 µm	Increase Aβ levels and deposition GSK3 signaling pathway altered Impaired cognitive tests	Zhuo, Portugal et al. 2010 14
	No folate, vitamin B6 or B12	8 months old	7 months	Increased from 6 µm to 28 µm	Increase Aβ level and deposition	Zhuo and Pratico 2010 55
	No folate, vitamin B6 or B12; Methionine 7.7g/kg	8 months old	7 months	Increased from 6 µm to over 150 µm	No change in Aβ levels	Zhuo and Pratico 2010 84
	Methionine 7.7g/kg	9 months old	5 months	Increased from 3 µm to 15 µm	2 months normal diet feeding restores the Hcy levels to normal, and slow Aβ deposition	Zhuo and Pratico 2010 76
TgCRND8	No folate, vitamin B6 or B12	15 days	45 days or 60 days	Increased from 0.2 µm to over 200 µm (45 days) or over 400 µm (60 days)	Increase Aβ level and deposition Increase PS1 and BACE1 mRNA and protein level expression	Fuso, Nicolia et al. 2008 11
					PSNE1 gene is regulated by HHcy	Fuso, Nicolia et al. 2009 107
					SAM treatment restores the methylation and oxidative system damaged by HHcy	Cavallaro, Fuso et al. 2010 108