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Possible role of d-serine in the pathophysiology of Alzheimer's disease

2003; Elsevier BV; Volume: 28; Issue: 2 Linguagem: Inglês

10.1016/j.pnpbp.2003.11.009

1878-4216

Kenji Hashimoto, Takeshi Fukushima, Eiji Shimizu, Shinichi Okada, Naoya Komatsu, Naoe Okamura, Kaori Koike, Hiroki Koizumi, Chikara Kumakiri, Kazuhiro Imai, Masaomi Iyo,

Tryptophan and brain disorders

Several lines of evidence suggest that d-serine may function as an endogenous agonist of the glycine site on the N-methyl-d-aspartate (NMDA) receptor that has been implicated in the pathophysiology of Alzheimer's disease (AD). The purpose of the study was to determine whether serum levels of d- and l-serine in patients with AD are altered as compared with normal controls. Serum levels of d- and l-serine in patients of AD and age- and gender-matched normal controls were determined using a high-performance liquid chromatography (HPLC). Serum levels of d-serine in the patients with AD were slightly (z=−1.77, p=0.078) lower than those of normal controls. In contrast, serum levels of l-serine in the patients were slightly (z=−1.73, p=0.083) higher than those of controls. In addition, the percentage (%) of d-serine in the total (l+d) serine in the patients was significantly (z=−2.36, p=0.018) lower than that of controls. The present study suggests that the reduced activity of serine racemase, an enzyme catalyzing the formation of d-serine from l-serine may play a role in the pathophysiology of AD.