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P2‐257: BIOTINIDASE AS A NOVEL BIOMARKER OF NEURAL CHANGES AND AD CSF BIOMARKERS ACROSS THE ALZHEIMER'S DISEASE SPECTRUM
Author(s) -
McLimans Kelsey E.,
Crank Kathleen,
Pappas Colleen,
Plagman Alexandra K.,
Wolf Tovah,
Klinedinst Brandon S.,
Le Scott T.,
Wang Qian,
Willette Auriel A.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2664
Subject(s) - biomarker , medicine , oncology , alzheimer's disease , neuroimaging , disease , endocrinology , psychology , biology , neuroscience , biochemistry
neurodegeneration or as potential biochemical correlates of cognitive decline. Neuronal pentraxin is a candidate synaptic biomarker that has been explored and validated using mass spectrometry. We thus wanted to evaluate the diagnostic accuracy of neuronal pentraxin 2 (NPTX2) in a retrospective study, its correlation with other neurodegenerative markers than tau and its relation with overall cognition (Mini-mental State Examination (MMSE). Methods: Research immunoassays for NPTX2 and neurofilament light (NfL) were established with a pair of newly developed monoclonal antibodies. Assays were qualified at the analytical levels with respect to sensitivity (measurable biomarker levels in all CSF samples), selectivity, precision, and dilutional linearity. NPTX2 and NfL levels were measured in age-matched controls (n1⁄420), subjects with Mild Cognitive Impairment (MCI, n1⁄438), and dementia due to AD (n1⁄450), in a cohort in which we previously determined CSF Neurogranin trunc P75 (Ng), BACE1, tau, Ab1-42, Ab1-40. Results: Analytical performance of NPTX2 and NfL were approved according to previously established performance criteria. In the clinical samples, decreased NPTX2 levels did not correlate to CSF-tau levels and were also not associated with NfL levels. Receiver operating curves (ROC) of NPTX2 can discriminate AD from controls (AUC: 0,724 6 0,049), but the area under the curve (AUC) was significantly higher for the NPTX2/tau ratio (0,851 6 0,066, p<0,05). In contrast to Ng or the Ng/BACE1 ratio, baseline MMSE scores in dementia due to AD and MCI groups combined were significantly correlated with NPTX2 and NPTX2/tau levels. Conclusions: Different synaptic markers may reflect different aspects of synaptic loss/dysfunction and may add diagnostic value to CSF-tau and CSF-Ab biomarker profiles. In particular this novel ELISA, based on monoclonal antibodies, may allow further larger prospective studies to determine the value of NPTX2 or NPTX2/tau as a biochemical correlate of longitudinal cognitive decline and clinical progression in AD.