Possible role of D-serine in the pathophysiology of Alzheimer's disease.
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.
Hashimoto
Kenji
K
Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan. hashimoto@faculty.chiba-u.ac.jp
Fukushima
Takeshi
T
Shimizu
Eiji
E
Okada
Shin-ichi
S
Komatsu
Naoya
N
Okamura
Naoe
N
Koike
Kaori
K
Koizumi
Hiroki
H
Kumakiri
Chikara
C
Imai
Kazuhiro
K
Iyo
Masaomi
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy; D014150:Antipsychotic Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule / Q000706:statistics & numerical data; D008875:Middle Aged; D019998:Racemases and Epimerases / Q000097:blood; D012694:Serine / Q000097:blood* / Q000737:chemistry; D018709:Statistics, Nonparametric; D000099300:Serine Racemase
D014150:Antipsychotic Agents; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase