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Urinary Homocysteic Acid Levels Correlate with Mini-Mental State Examination Scores in Alzheimer's Disease Patients

Article type: Research Article

Authors: Hasegawa, Tohrua; * | Ichiba, Masayoshib | Matsumoto, Shin-eic | Kasanuki, Kojid | Hatano, Takuc | Fujishiro, Hiroshiged | Iseki, Eizod | Hattori, Nobutakac | Yamada, Tatsuoe | Tabira, Takeshic

Affiliations: [a] Saga Woman Junior College, Saga, Japan | [b] Social Medicine, Faculty of Medicine, Saga University, Saga, Japan | [c] Department of Neurology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan | [d] PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, Koto-ku, Tokyo, Japan | [e] Department of Neurology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

Correspondence: [*] Correspondence to: Tohru Hasegawa, Social Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 840-8502, Japan. Tel.: +81 952 34 2289; E-mail: hasegawa@yumekobo-shizuka.com.

Keywords: Aging, Alzheimer disease, homocysteic acid, MMSE, smoking, uremia

DOI: 10.3233/JAD-2012-120022

Journal: Journal of Alzheimer's Disease, vol. 31, no. 1, pp. 59-64, 2012

Accepted 22 March 2012
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Published: 5 July 2012
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Supplementary Materials:

Supplementary Materials.

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.

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