Abstract
The identification of diagnostic-prognostic biomarkers of dementia has become a global priority due to the prevalence of neurodegenerative diseases in aging populations. The objective of this study was to assess the diagnostic performance of cerebrospinal fluid (CSF) biomarkers across patients affected by either Alzheimer’s disease (AD), tauopathies other than AD (TP), or vascular dementia (VD), and cognitively normal subjects (CNS). One hundred fifty-three patients were recruited and tested for classical AD CSF biomarkers- Amyloid-ß42 and tau proteins - and novel candidate biomarkers - neurofilament (NF-) light and microRNA (miR) -21, -125b, -146a, and -222.All dementia patients had significantly higher concentrations of NF-light compared to CNS, with the TP group displaying the highest NF-light values. A significant inverse correlation was also observed between NF-light and cognitive impairment. Of the four miRNAs analyzed, miR-222 levels were significantly increased in VD patients compared to both CNS and AD. In addition, while NF-light showed a better diagnostic performance than miR-222 and classical AD biomarkers in differentiating TP and VD from CNS, classical AD biomarkers revealed higher performance in discriminating AD from non-AD disorders.Overall, our results suggest that CSF NF-light and miR-222 are promising biomarkers that may help to diagnose non-AD disorders.
Highlights
The constant rate of increase in global life expectancy and the consequent rise in the average age of the population have been accompanied by a significant surge in the incidence of the most common age-related diseases (ARDs), including neurodegenerative diseases [1]
Our results showed that cerebrospinal fluid (CSF) NF-light levels increased in all analyzed groups of patients with dementia compared to cognitively normal subjects (CNS)
The TP group was characterized by the highest NF-light values, which, in turn, showed a better diagnostic performance than classical Alzheimer’s disease (AD) biomarkers in distinguishing TP from CNS
Summary
The constant rate of increase in global life expectancy and the consequent rise in the average age of the population have been accompanied by a significant surge in the incidence of the most common age-related diseases (ARDs), including neurodegenerative diseases [1]. The economic costs and social burden associated with neurodegenerative diseases have motivated efforts to identify innovative biomarkers for accurate and timely diagnosis and effective treatments. Neurodegenerative diseases include Alzheimer's disease (AD), the most common form of dementia, and non-Alzheimer’s diseases (NAD), a group of disorders that account for approximately 30-40 per cent of dementias worldwide [2]. AD diagnosis is currently based on clinical evaluation, neuropsychological testing, neuro-imaging techniques, and cerebrospinal fluid (CSF) classical biomarkers [3,4,5,6]. Three core CSF biomarkers, e.g. Amyloid-ß42 (Aß42), total tau (t-tau) and phosphorylated tau (p-tau) proteins, have been included in the diagnostic criteria of AD, and could be relevant for differential diagnosis [3]. A recent Cochrane review suggested that they have a better sensitivity than specificity, performing best in ruling out AD [5]
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