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S084-4

D-Serine Levels In Alzheimer’S Disease: Implications for Novel Biomarker
Development

Rogerio Panizzutti

Federal University of Rio de Janeiro, Brazil

Background/Objective: 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.

Method: Here, we first measured D-serine levels in postmortem hippocampal and cortical samples
from non-demented 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
to 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.

Result: 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. Increased brain and CSF D-serine levels are associated with
Alzheimer’s disease.

Conclusion: Inhibition of DAAO by sodium benzoate to enhance NMDAR-mediated
neurotransmission may improve cognitive function of patients with schizophrenia or early-phase AD.

Reference: Madeira, C. ; Mychael Lourenco ; Vargas-Lopes, C. ; Claudia Suemoto ; Carlos Otávio
Brandão ; Taylor Reis ; Renata Leite ; Jerson Laks ; Wilson Jacob-Filho ; Carlos Pasqualucci ; Lea
Grinberg ; Sergio Ferreira ; Panizzutti, R. . D-serine levels in Alzheimer's disease: Implications for
novel biomarker development. Translational Psychiatry, in press.
Brito-Moreira, Jordano, LIMA, Andréa C Paula, Bomfim, Theresa R., Oliveira, Fabio F., Sepulveda
FJ, MELLO, F. G., Panizzutti, R., Ferreira, Sergio T. Ab Oligomers Induce Glutamate Release from
Hippocampal Neurons. Current Alzheimer Research. , v.8, p.552