title: Urinary homocysteic acid levels correlate with mini-mental state examination scores in Alzheimer's disease patients.
abstract: Homocysteic acid (HA) has been suggested as a pathogen in a mouse model of Alzheimer's disease (AD), 3xTg-AD. However, it is not established whether HA is involved in humans. We investigated the relationship between urinary HA levels and Mini-Mental State Examination (MMSE) scores in AD patients (n = 70) and non-AD controls (n = 34). We found a positive, statistically significant relationship between the two variables (the urinary HA level and MMSE score) (r = 0.31, p = 0.0008, n = 70). This relationship was stronger in females than males (r = 0.43, p = 0.005, n = 44 in females; r = 0.48, p = 0.02, n = 22 in males). The urinary HA levels were significantly different in AD patients than controls (AD: 8.7 ± 7.5, n = 70; non-dementia control: 13.3 ± 9.4, n = 34, p < 0.01). In addition, aging and smoking were found as lowering factors for urinary HA levels. Our preliminary study showed a negative, statistically significant relationship between blood HA (micromole) and urine HA levels (r = -0.6, p = 0.007, n = 19), and between blood HA levels and MMSE scores (r = -0.79, p = 0.0000518, n = 19). On the basis of these results, we speculate that reduced urinary excretion induces elevated HA levels in blood, resulting in cognitive dysfunctions. This study also suggests that HA may be a candidate of neurotoxins for uremic encephalopathy. Since amyloid-β increases HA toxicity and HA is an agonist of N-methyl-D-aspartic acid (NMDA) receptor, we speculate that elevated blood HA affects the brain cognitive function through NMDA receptor-mediated toxicity in AD.
authors.affiliation: Saga Woman Junior College, Saga, Japan. hasegawa@yumekobo-shizuka.com
authors.forename: Tohru
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ichiba
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Matsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Kasanuki
authors.forename: Taku
authors.initials: T
authors.lastname: Hatano
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Fujishiro
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tabira
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D012907:Smoking / Q000652:urine; D013223:Statistics as Topic
chemical_list: D006710:Homocysteine; C007956:homocysteic acid