Fluid Biomarkers in Alzheimer’s Disease and Other Neurodegenerative Disorders: Toward Integrative Diagnostic Frameworks and Tailored Treatments
Linda Giampietri,
Elisabetta Belli,
Maria Francesca Beatino,
Sara Giannoni,
Giovanni Palermo,
Nicole Campese,
Gloria Tognoni,
Gabriele Siciliano,
Roberto Ceravolo,
Ciro De Luca,
Filippo Baldacci
Affiliations
Linda Giampietri
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Elisabetta Belli
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Maria Francesca Beatino
Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Sara Giannoni
Neurology Unit, Ospedale San Giuseppe, 50053 Empoli, Italy
Giovanni Palermo
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Nicole Campese
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Gloria Tognoni
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Gabriele Siciliano
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Roberto Ceravolo
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Ciro De Luca
Laboratory of Morphology of Neuronal Network and Systems Biology, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy
Filippo Baldacci
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer′s Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.