Format

Send to

Choose Destination
Transl Psychiatry. 2015 May 5;5:e561. doi: 10.1038/tp.2015.52.

d-serine levels in Alzheimer's disease: implications for novel biomarker development.

Author information

1
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
2
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
3
Discipline of Geriatrics, University of São Paulo Medical School, Sao Paulo, Brazil.
4
Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
5
Department of Pathology, University of São Paulo Medical School, Sao Paulo, Brazil.
6
1] Department of Pathology, University of São Paulo Medical School, Sao Paulo, Brazil [2] Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
7
1] Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil [2] Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
8
1] Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil [2] Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-β oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-β/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis.

PMID:
25942042
PMCID:
PMC4471283
DOI:
10.1038/tp.2015.52
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center