Cerebrospinal Fluid ‘Neuronal Thread Protein’ Comes from Serum by Passage over the Blood-Brain Barrier

Cerebrospinal fluid (CSF) biochemical markers for Alzheimer's disease (AD) would be of great value, both to improve clinical diagnostic accuracy and to increase our knowledge of the pathogenesis of the disorder. An increase in the CSF-level of ‘neuronal thread protein’ (pancreatic thread protein (PTP) immunoreactive material in the brain) has been suggested to be just such a biochemical marker. We have studied CSF ‘neuronal thread protein’-like immunoreactivity (NTPLI) using a microparticle enzyme immunoassay. CSF-NTPLI did not differ significantly between AD type I (pure AD) and controls, but was significantly higher in AD type II (senile dementia) and vascular dementia (VAD) as compared with controls. Signs of blood-brain barrier (BBB) damage (elevated CSF/S albumin ratio) were found in both AD type II and in VAD, but not in AD type I. In a multiple ANOVA, with age and CSF/S albumin ratio as covariates, no significant difference in CSF-NTPLI between diagnostic groups was noted though both CSF/S albumin ratio and age (P<0.0001 andP<0.001 respectively) were found to influence the CSF-NTPLI level. Since BBB function was found to influence the CSF-NTPLI level, we examined whether NTPLI was present in serum. Indeed, serum NTPLI was about 40 times higher than CSF-NTPLI in neurological patients. Moreover, there was a statistically significant correlation between S-NTPLI and CSF-NTPLI. Taken together, present findings suggest that most of NTPLI in CSF comes from the serum, by passage over the BBB. As with the IgG index, we created a ‘NTPLI index’ (CSF/S NTPLI divided by CSF/S albumin ratio) to evaluate if there was an increase in NTPLI locally produced within the CNS in AD. However, there were no significant differences in NTPLI index between any of the groups. These findings suggest that, using these antibodies, CSF-NTPLI has no potential as a biochemical marker for AD, and that it is important to consider confounding factors, such as BBB function, in CSF studies.