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d -Serine acts as a co-agonist of  N -methyl- d -aspartate receptors (NMDAR) which appear overactivated in AD, while  d -aspartate is a modulatory molecule acting on NMDAR as a second agonist. The aim of this work is to clarify whether the levels of these  d -amino acids in serum are deregulated in AD, with the final goal to identify novel and precocious biomarkers in AD. Serum levels of  l - and  d -enantiomers of serine and aspartate were determined by HPLC using a pre-column derivatization procedure and a selective enzymatic degradation. Experimental data obtained from age-matched healthy subjects (HS) and AD patients were statistically evaluated by considering age, gender, and disease progression, and compared. Minor changes were apparent in the serum  l - and  d -aspartate levels in AD patients compared to HS. A positive correlation for the  d -serine level and age was apparent in the AD cohort. Notably, the serum  d -serine level and the  d -/total serine ratio significantly increased with the progression of the disease. Gender seems to have a minor effect on the levels of all analytes tested. This work proposes that the serum  d -serine level and  d -/total serine ratio values as novel and valuable biomarkers for the progression of AD: the latter parameter allows to discriminate CDR 2 and CDR 1 patients from healthy (CDR 0) individuals.

Serum d-serine levels are altered in early phases of Alzheimer’s disease: towards a precocious biomarker