This thesis presents a multidisciplinary approach to improve Alzheimer’s disease (AD) early diagnosis and therapy. The first part, based on the PRAMA cohort, identifies two novel CSF biomarkers using biophysical and cell viability assays to detect proteostasis failure. The second part focuses on the single-domain antibody DesAb-O, demonstrating its ability to selectively detect Aβ42 oligomers and neutralize their toxicity in patient-derived CSF. This tool was further engineered into Dimeric-DesAb-O. In the third part, ELISA, ThT, and TEM analyses confirm that dimerization enhances binding avidity, alters fibril morphology, and increases protective efficacy at low concentrations. This study suggests innovative immunodiagnostic and therapeutic strategies for future AD clinical applications.
- ORCID: 0009-0004-3087-286X
Liliana Napolitano
First Section: Putative CSF biomarkers of Alzheimer’s disease based on the novel concept of generic protein misfolding and proteotoxicity: the PRAMA cohortpp.65-77
Liliana Napolitano
Second Section: A single domain antibody detects and neutralises toxic Aβ42 oligomers in the Alzheimer’s disease CSFpp.79-93
Liliana Napolitano
Third Section: Design of a dimeric-nanobody specific for Aβ42 oligomers: the Dimeric-DesAb-Opp.95-115
Titolo del libro
A multidisciplinary approach for the early diagnosis of Alzheimer’s disease and potential therapeutic applications
Autori
Liliana Napolitano
Opera sottoposta a peer review
Numero di pagine
184
Anno di pubblicazione
2026
Copyright
© 2026 Author(s)
Licenza d'uso
Licenza dei metadati
Editore
Firenze University Press
DOI
10.36253/979-12-215-0993-9
ISBN Print
979-12-215-0992-2
eISBN (pdf)
979-12-215-0993-9
eISBN (xml)
979-12-215-0994-6
Collana
Premio Tesi di Dottorato Città di Firenze
ISSN della collana
3103-3881
e-ISSN della collana
3103-3989