Clinical application and usability of Blood Biomarkers as screening tool in Alzheimer disease: a Validation Study

Dementia due to neurodegenerative diseases affects over 50 million people worldwide. Alzheimer¿s disease (AD) is the most common cause, placing a significant social and economic burden on National Health Systems. Early and accurate diagnosis of AD in clinical practice is still a major challenge. However, it is crucial to promote early prevention and intervention strategies, considering that recent evidence suggests disease-modifying therapies may be more effective in the early stages. Although established biomarkers such as cerebrospinal fluid (CSF) analysis and Amyloid PET imaging can provide an objective measure of AD pathology in vivo, their use is still limited due to cost, invasiveness, and contraindications. These obstacles are limiting the wide dissemination of screening programs to assess individuals at risk for dementia.
Recent advances in ultrasensitive detection methods for blood biomarkers of amyloidopathy, tauopathy, and neurodegeneration offer promising results that could pave the way for a breakthrough in the field. Moreover, accumulating evidence suggests that the study of biomarkers of neuroinflammation may provide new insight into the complex relations between AD pathogenetic processes, disease severity, and clinical progression.
The main hypothesis of this project is that novel plasma biomarkers may have the potential to change the diagnostic process of neurodegenerative diseases, reducing the need for unnecessary analyses and providing valuable information from a clinical and public health perspective. In the future, blood biomarkers may serve as a first-level screening tool before second level analyses such as CSF analysis and PET imaging, leading to earlier diagnosis and treatment interventions. The aims of this project are:
a)to evaluate concordance between plasma and CSF biomarkers for AD in a multicenter population of consecutive subjects with cognitive disorders who are candidate for CSF analysis for clinical practice in specialised Italian Centers for Cognitive Disorders and Dementias (CCDDs), assessing the accuracy of plasma biomarkers in distinguishing individuals with CSF evidence of AD pathology;
b)to establish the diagnostic performance and identify optimal cut-offs of a combination of plasma biomarkers of neurodegeneration and neuroinflammation with respect to clinical diagnosis of AD and mild cognitive impairment (MCI) due to AD through a cross-sectional study in a group of CCDDs from the three major macro-areas of Italy (North, Center, South); c)to evaluate the diagnostic and prognostic performance of previously established plasma biomarkers cut-offs using data from a population-based cohort study conducted in a community-dwelling population: the Zabut Aging Project (ZAP). The validation of these novel biomarkers for AD could facilitate a paradigm shift in clinical practice towards the implementation of reliable and cost-effective diagnostic tools, which can be used not only for research purposes but also in clinical practice. The validation and use of plasma biomarker cut-offs may create opportunities for population-based interventions, reduce unnecessary investigations in individuals at low risk for dementia, and enable broader and more rapid access to diagnosis and disease-modifying treatments for subjects in the AD continuum, with significant positive economic and social implications for National Health Systems as well as for individuals affected by a neurodegenerative disease or their caregivers.