Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer’s disease

Abstract

Background Alzheimer’s disease (AD) is the most prevalent form of dementia. Currently, the most studied biomarkers of AD are cerebrospinal fluid (CSF) amyloid β 1-42, total tau and phosphorylated tau. However, misdiagnosis can exceed 20%. Recently, we found that CSF amyloid β precursor-like protein-1 (APLP1) and neuronal pentraxin receptor (NPTXR) are promising biomarkers of AD. The aim of the present study is to validate CSF APLP1 and NPTXR as biomarkers of AD severity. Methods APLP1 and NPTXR concentrations were measured in the CSF of patients with mild cognitive impairment (MCI) (n = 14), mild AD (n = 21), moderate AD (n = 43) and severe AD (n = 30) using enzyme-linked immunosorbent assays (ELISAs). Results CSF APLP1 and NPTXR were not associated with age or sex. CSF APLP1 was not different between any of the AD severity groups (p = 0.31). CSF NPTXR was significantly different between MCI and mild AD (p = 0.006), mild and moderate AD (p = 0.016), but not between moderate and severe AD (p = 0.36). NPTXR concentration progressively declined from MCI to mild, to moderate and to severe AD patients (p < 0.0001, Kruskal-Wallis test). CSF NPTXR positively correlated with the Mini-Mental Status Examination (MMSE) score (p < 0.001). Conclusions NPTXR concentration in CSF is a promising biomarker of AD severity and could inform treatment success and disease progression in clinical settings.

Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion

“…NPTXR is a transmembrane synaptic protein belonging to the neuronal pentraxin family. NPTXR plays a role in organisation of excitatory and inhibitory synapses by interaction with neuronal pentraxin 1 and 236 and lower CSF levels were also reported for Alzheimer’s disease and multiple sclerosis 37 38. Interestingly, NPTXR levels were not significantly altered in sFTD cases compared with non-neurodegenerative controls in our study, although we observed a trend to lower CSF levels.…”

Fluid Biomarkers for Synaptic Dysfunction and Loss

“…233,234 All 3 neuronal pentraxins have lately received much attention and have been shown in several studies to have decreased CSF levels in AD and MCI groups compared with controls. 231,[235][236][237][238][239][240][241][242] CSF pentraxin levels also correlate with cognitive performance and hippocampal volume. 150,242,243 Few studies have been performed on other diseases but NPTXR has also been associated with other neurological diseases such as MS 244 and FTD.…”

Alterations in Self-Aggregating Neuropeptides in Cerebrospinal Fluid of Patients with Parkinsonian Disorders

“…NPTX1 and NPTX2 are secreted from presynaptic membranes, form oligomeric complexes with NPTXR, and bind extracellular matrix proteins and regulate clustering of neurotransmitter receptors [25]. NPTX1 has been shown to decrease in AD CSF by targeted MS/MS [26] and NPTXR during AD progression [27,28]. NPTX1 and NPTXR have been shown to decrease in CSF from patients with atypical parkinsonian disorders [19].…”