OLFACTORY BULB PROTEOMIC ALTERATIONS IN PARKINSON’S DISEASE PROGRESSION: ALZHEIMER’S DISEASE COPATHOLOGY INVOLVEMENT

Parkinson's disease (PD) is a neurodegenerative disorder that goes beyond motor dysfunction such as dysautonomia and cognitive impairment. Neuropathologically, it is characterized by α-synuclein aggregates. However, increasing evidence indicates that PD frequently presents concomitantly with Alzheimer's disease (AD) proteinopathy, including amyloid-β and tau aggregates. This synergistically contributes to enhancing inflammation and pathology, accelerating clinical progression. These proteinopathies also affect regions distal to their primary sites, including the olfactory bulb (OB), a vulnerable region associated with early non-motor manifestations such as hyposmia. This study aims to analyze PD pathology across early, intermediate, and advanced stages of AD associated copathology. A total of 103 human OB samples diagnosed with PD and AD were obtained from national and international biobanks. Experimental groups have been created based on neuropathological diagnosis, including samples from donors in different Braak α-syn (1-6) and Braak tau (I–VI) pathological stages progression (early, intermediate, and advanced stages), with all possible combinations of copathology. Protein quantification was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Bioinformatic analysis included protein expression, metabolic pathways and protein interaction networks. Proteomic analysis identified 30,297 peptides and 5,495 proteins. Early findings suggest differential protein expression across PD pathology associated with AD progression. Funded by 2025-GRIN-38350, PID2019-108659RB-I00, and SBPLY/24/180225/000065. APFT is the beneficiary of a predoctoral contract funded by UCLM/ESF+. We acknowledge donors, the Spanish and Netherland Biobanks for their generous contribution.