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 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.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/analysis , C-Reactive Protein/analysis , Nerve Tissue Proteins/analysis , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Protein Precursor/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , C-Reactive Protein/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/diagnosis , Disease Progression , Female , Greece , Humans , Liquid Biopsy/methods , Male , Middle Aged , Nerve Tissue Proteins/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , tau Proteins/cerebrospinal fluidABSTRACT
Cognitive impairment is a common phenomenon in multiple sclerosis (MS), occurring at all stages of the disease, even at the earliest, and can be a major source of disability, social impairment, and impoverished quality of life. Cognitive dysfunction is mainly focused on working memory, conceptual reasoning, verbal fluency, speed of information processing, attention and executive function. Additional clinical factors, including disease course, fatigue and affective disturbance, can impact the degree of MS-related cognitive impairment. We present the results from the two-phases of our prospective study on cognitive decline in MS patients using the data collected from the A' Neurologic clinic at AHEPA hospital, Thessaloniki, Greece. Most of the patients of the present study revealed mild cognitive impairment with mild influence on the everyday function. We found weak correlation between cognitive deficit and the duration of MS, as well as the physical disability status and moderate correlation between cognitive impairment and the type of the disease as well as MRI findings (atrophy and lesion load). Our results also indicate that the currently available battery of neuropsychological tests: California Verbal Learning test (CVLT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test and Paced Auditory Serial Addition Test (PASAT) can be used as a reliable tool in the diagnosis of cognitive deficits of MS patients, as related to their degree of disability and to the type of their disease. Evaluation of cognitive functions should be incorporated in the regular assessment and monitoring of MS patients since they seem to be well correlated with the progression of the disease.
