Might Fibroblasts from Patients with Alzheimer’s Disease Reflect the Brain Pathology? A Focus on the Increased Phosphorylation of Amyloid Precursor Protein Tyr(682) Residue

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no cure and no effective diagnostic criteria. The greatest challenge in effectively treating AD is identifying biomarkers specific for each patient when neurodegenerative processes have not yet begun, an outcome that would allow the design of a personalised therapeutic approach for each patient and the monitoring of the therapeutic response during the treatment. We found that the excessive phosphorylation of the amyloid precursor protein (APP) Tyr(682) residue on the APP (682)YENPTY(687) motif precedes amyloid β accumulation and leads to neuronal degeneration in AD neurons. We proved that Fyn tyrosine kinase elicits APP phosphorylation on Tyr(682) residue, and we reported increased levels of APP Tyr(682) and Fyn overactivation in AD neurons. Here, we want to contemplate the possibility of using fibroblasts as tools to assess APP Tyr(682) phosphorylation in AD patients, thus making the changes in APP Tyr(682) phosphorylation levels a potential diagnostic strategy to detect early pathological alterations present in the peripheral cells of AD patients’ AD brains.