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

Background Alzheimer's disease (AD) is the most prevalent form of dementia. Currently, the most studied biomarkers of AD are cerebrospinal fluid (CSF) amyloid ß 1-42, total tau and phosphorylated tau. However, misdiagnosis can exceed 20%. Recently, we found that CSF amyloid ß 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.

Assessment of Atherosclerosis in Ischemic Stroke by means of Ultrasound of Extracranial/Intracranial Circulation and Serum, Urine, and Tissue Biomarkers.

It is a common practice to take into consideration age, diabetes, smoking, treated and untreated systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol for the prediction of atherosclerosis and stroke. There are, however, ultrasound markers in use for the assessment of atherosclerosis and the evaluation of stroke risk. Two areas of investigation are of interest: the carotid artery and the intracranial arterial circulation. Again, within the domain of the carotid artery, two ultrasonic markers have attracted our attention: intima media thickness of the carotid artery and the presence of carotid plaque with its various focal characteristics. In the domain of intracranial circulation, the presence of arterial stenosis and the recruitment of collaterals are considered significant ultrasonic markers for the above-mentioned purpose. On the other hand, a series of serum, urine, and tissue biomarkers are found to be related to atherosclerotic disease. Future studies might address the issue of whether the addition of proven ultrasonic carotid indices to the aforementioned serum, urine, and tissue biomarkers could provide the vascular specialist with a better assessment of the atherosclerotic load and solidify their position as surrogate markers for the evaluation of atherosclerosis and stroke risk.