Relationship between ß-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease.

ABSTRACT

BACKGROUND: Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear. OBJECTIVE: To study six CSF biomarkers in a clinical cohort of patients with different neurodegenerative conditions. METHODS: We measured markers of amyloid-ß protein precursor (AßPP) processing (Aß42, sAßPPß, ß-secretase activity), neuronal damage (total tau, p-tau), and inflammation (YKL-40) in CSF from 194 participants with the following diagnoses subjective cognitive impairment or non-amnestic mild cognitive impairment (na-SCI, n = 44), amnestic mild cognitive impairment (aMCI, n = 45), dementia of the Alzheimer type (DAT, n = 59), frontotemporal dementia (FTD, n = 22), and 24 cognitively normal controls. We compared biomarkers between clinical groups and CSF-profile groups, and we analyzed the correlation between biomarkers. RESULTS: CSF levels of sAßPPß were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aß42 correlated positively with ß-secretase activity (RS = 0.262) and sAßPPß (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAßPPß contributed significantly to distinguish DAT from FTD. CONCLUSIONS: CSF biomarkers of AßPP processing correlate with each other and are decreased in FTD. The inflammatory marker YKL-40 is increased in different neurodegenerative diseases, even in early stages, and it correlates with biomarkers of neurodegeneration. This suggests that inflammation is a common feature in AD and FTD. A combination of CSF biomarkers tracking distinct pathophysiological processes may be useful to classify subjects with neurodegenerative conditions.