N-epsilon(gamma-glutamyl)lysine in cerebrospinal fluid marks Alzheimer type and vascular dementia

N-epsilon(gamma -glutamyl)lysine isodipeptide is released from the breakdow n of proteins cross-linked by transglutaminase enzymes. Transglutaminase ac tivation is a marker of apoptosis and elevated isodipeptide concentrations in body fluids might correlate with the intensity of apoptotic cell turnove r. The concentration of N-epsilon(gamma -glutamyl)lysine was measured in th e cerebrospinal fluid (CSF) of patients with probable Alzheimer's disease ( n = 14) and vascular type dementia (n = 11) and compared with not demented surgical controls (n = 17). Baseline levels of 26-62 nM/l (mean 37.9 +/- 8. 7 SD) free isodipeptide were detected in control patients. CSF isodipeptide levels showed significant elevation in vascular (mean 95.6 +/- 45.1 SD) as well as Alzheimer patients (176.6 +/- 77.1 SD). Isodipeptide concentration s above 120 nM/l were 72% specific and 77% sensitive to Alzheimer's dementi a, although the difference between the two dementias was statistically insi gnificant (p > 0.05). Determination of CSF N-epsilon(gamma -glutamyl)lysine isodipeptide concentration offers a novel method for measurement of neurod egeneration in primary and mixed dementias. (C) 2001 Elsevier Science Inc. All rights reserved.