Free d-amino acids in human cerebrospinal fluid of alzheimer disease, multiple sclerosis, and healthy control subjects

This is the first report of the presence of free D-amino acids in lumbar and ventricular human cerebrospinal fluid (CSF) of individuals with Alzheimer disease (AD) compared with CSF of normal control subjects and with individuals affected by multiple sclerosis, as an unrelated neurologic disorder. Free d-amino acids are present at significantly higher levels in AD CSF than normal CSF, whereas in the CSF of patients affected by multiple sclerosis, d-amino acids occurs at the same level as in the normal controls. The total d-amino acid content in ventricular CSF was 1.48 times higher in the AD than controls (26.4 vs 17.9 nmol/mL, p=0.025). The total d-amino acid content was 1.43 times higher in AD lumbar CSF than controls (1.89 vs. 1.32 nmol/mL, p=0.001). d-Aspartate in particular was 2.74 times higher in AD ventricular CSF compared to normal ventricular CSF (3.34 vs 1.22 nmol/mL, p=0.029). In lumbar CSF, d-aspartate was 1.5 times higher in AD than controls (0.054 vs 0.036 nmol/mL, p=0.041). Previously we reported that d-amino acids are elevated in AD brain proteins associated with neurofibrillary tangles compared to normal brain proteins (D'Aniello et al., 1992c; Fisher et al., 1992a,b). Thus, the d-amino acids present in CSF may originate from degradation of brain proteins.