Cerebrospinal fluid and serum D-serine concentrations are unaltered across the whole clinical spectrum of Alzheimer's disease

Tommaso Nuzzo, M. Miroballo, Alessia Casamassa, Andrea Mancini, Lorenzo Gaetani, Robert Nisticò, Paolo Eusebi, Masumi Katane, Hiroshi Homma, Paolo Calabresi, Francesco Errico, Lucilla Parnetti, Alessandro Usiello

Research output: Contribution to journalArticlepeer-review


The diagnosis of Alzheimer's disease (AD) relies on the presence of amyloidosis and tauopathy, as reflected in cerebrospinal fluid (CSF), independently from the clinical stage. Recently, CSF D-serine has been proposed as a possible new AD biomarker, reflecting dysfunctional activation of neuronal glutamatergic N-methyl-D-aspartate receptor (NMDAR). In this study, we measured blood serum and CSF concentration of two NMDAR modulators, such as D-serine and D-aspartate, in a cohort of drug-free subjects encompassing the whole AD clinical spectrum. In addition, we also analyzed D-serine levels in a cohort of post-mortem AD and control cortex samples. We reported unaltered serum and CSF concentrations of D-serine and D-aspartate in AD patients both during the AD progression and compared to non-demented controls. Accordingly, no correlation was detected between serum or CSF D-serine content and mini-mental state examination or Clinical Dementia Rating. Similarly, cortical D-serine levels were also unaltered in post-mortem samples of AD patients. Overall, our results failed to confirm previous findings indicating the CSF D-serine as a novel biomarker for AD.

Original languageEnglish
Article number140537
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number12
Publication statusPublished - Dec 2020


  • Alzheimer's disease
  • Biomarker
  • D-amino acids
  • Dementia
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology


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