BACKGROUND: Plasma homocysteine is elevated in Alzheimer's disease, but little is known regarding levels of related aminothiols in the disease. We therefore determined total plasma homocysteine, cysteine, and glutathione levels in patients and control subjects and investigated their relationship with cognitive scores. METHODS: We performed a prospective, case-controlled survey based in two UK Psychogeriatric Assessment Centres. Fifty patients with features compatible with DSM-IV criteria for primary degenerative dementia of Alzheimer type were recruited together with 57 cognitively intact age- and gender-matched control subjects. Mini-Mental State and Alzheimer's Disease Assessment Scale-Cognitive Subsection (ADAS-Cog) scores were determined for patients and control subjects. Aminothiols were assayed with an automated high-performance liquid chromatography (HPLC) system. RESULTS: Patients had significantly elevated total plasma homocysteine (p <.001) and cysteine (p <.01), but there were no group differences for total plasma glutathione. Glutathione was, however, a highly significant and independent predictor of cognitive scores in patients (p =.002); lower plasma levels were associated with more severe cognitive impairment. CONCLUSIONS: Total plasma homocysteine and cysteine are elevated in Alzheimer's disease, suggesting intact transsulphuration but defective remethylation of homocysteine in the disease. Total plasma glutathione levels in patients correlate with cognitive scores. Taken together, these observations perhaps reflect the differential effects of Alzheimer's disease-related oxidative stress on the two key pathways of homocysteine metabolism.
BACKGROUND: Plasma homocysteine is elevated in Alzheimer's disease, but little is known regarding levels of related aminothiols in the disease. We therefore determined total plasma homocysteine, cysteine, and glutathione levels in patients and control subjects and investigated their relationship with cognitive scores. METHODS: We performed a prospective, case-controlled survey based in two UK Psychogeriatric Assessment Centres. Fifty patients with features compatible with DSM-IV criteria for primary degenerative dementia of Alzheimer type were recruited together with 57 cognitively intact age- and gender-matched control subjects. Mini-Mental State and Alzheimer's Disease Assessment Scale-Cognitive Subsection (ADAS-Cog) scores were determined for patients and control subjects. Aminothiols were assayed with an automated high-performance liquid chromatography (HPLC) system. RESULTS:Patients had significantly elevated total plasma homocysteine (p <.001) and cysteine (p <.01), but there were no group differences for total plasma glutathione. Glutathione was, however, a highly significant and independent predictor of cognitive scores in patients (p =.002); lower plasma levels were associated with more severe cognitive impairment. CONCLUSIONS: Total plasma homocysteine and cysteine are elevated in Alzheimer's disease, suggesting intact transsulphuration but defective remethylation of homocysteine in the disease. Total plasma glutathione levels in patients correlate with cognitive scores. Taken together, these observations perhaps reflect the differential effects of Alzheimer's disease-related oxidative stress on the two key pathways of homocysteine metabolism.
Authors: Camden M Driggers; Kelsey M Kean; Lawrence L Hirschberger; Richard B Cooley; Martha H Stipanuk; P Andrew Karplus Journal: J Mol Biol Date: 2016-07-29 Impact factor: 5.469
Authors: Paul J Derry; Muralidhar L Hegde; George R Jackson; Rakez Kayed; James M Tour; Ah-Lim Tsai; Thomas A Kent Journal: Prog Neurobiol Date: 2019-10-08 Impact factor: 11.685
Authors: Adam C Naj; Gary W Beecham; Eden R Martin; Paul J Gallins; Eric H Powell; Ioanna Konidari; Patrice L Whitehead; Guiqing Cai; Vahram Haroutunian; William K Scott; Jeffery M Vance; Michael A Slifer; Harry E Gwirtsman; John R Gilbert; Jonathan L Haines; Joseph D Buxbaum; Margaret A Pericak-Vance Journal: PLoS Genet Date: 2010-09-23 Impact factor: 5.917
Authors: Maria Kovalska; Barbara Tothova; Libusa Kovalska; Zuzana Tatarkova; Dagmar Kalenska; Anna Tomascova; Marian Adamkov; Jan Lehotsky Journal: Neurochem Res Date: 2018-07-12 Impact factor: 3.996