Clinical Application and Usability of Blood Biomarkers As Screening Tool in Alzheimer Disease: a Validation Study

Dementia caused by neurodegenerative diseases affects over 50 million people worldwide, Alzheimer's disease (AD) being the most common cause. As life expectancy increases, the prevalence of these diseases is expected to grow in coming decades, placing a significant social and economic burden on National Health Systems. AD is pathologically defined by two major hallmarks: amyloid-ß (Aß) accumulation in extracellular plaques, and hyperphosphorylated tau (p-tau) accumulation in intracellular neurofibrillary tangles. In recent decades, increased understanding of AD pathophysiology and technological advancements have allowed the development of new techniques providing an objective measure of AD pathological processes in vivo. Established biomarkers such as those obtained by cerebrospinal fluid (CSF) examination and positron emission tomography (PET) measures have been progressively introduced into clinical practice, consistently with the most recent NIA-AA diagnostic criteria. However, the widespread use of these methods remains limited due to their low availability, perceived invasiveness, high costs, and contraindications. Accordingly, there is a pressing need for costeffective biomarkers that can be less invasively obtained. Therefore, recent promising results in the development of ultrasensitive detection methods for blood biomarkers could facilitate a breakthrough in the field, simplifying and accelerating the diagnostic process of subjects with cognitive decline. The main hypothesis of this study is that new plasma biomarkers of amyloidopathy, tauopathy, neurodegeneration, measured through a novel CLEIA methodology, may have the potential to change the diagnostic process of neurodegenerative diseases by reducing the need for unnecessary exams thus providing valuable information from a clinical and public health perspective. The larger availability and easier procedures for obtaining AD biomarkers from plasma, as compared to CSF, may also help to reduce territorial