Affiliations: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain
Correspondence:
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Correspondence to: Alberto Lleó, MD, PhD, Department of Neurology, Hospital Sant Pau, Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain. Tel.: +34 935565986; Fax: +34 935565602; E-mail: alleo@santpau.es.
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-β protein precursor (AβPP) processing (Aβ42, sAβPPβ, β-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 sAβPPβ were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aβ42 correlated positively with β-secretase activity (RS = 0.262) and sAβPPβ (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAβPPβ contributed significantly to distinguish DAT from FTD. Conclusions:CSF biomarkers of AβPP 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.
