Leader: Angelo Antonini (UNIPD); Other collaborator(s): Benedetta Nacmias (UNIFI); Stefano Salvioli (UNIBO); Carlo Pappone, Patrizia Rovere-Querini (UniSR); Licia Iacoviello (NEUROMED); Maria Benedetta Donati (NEUROMED); RTDA PNRR TBA (UNICATT); Emanuele Marzetti (UNICATT)
The general objective is that of the identification of markers (imaging and soluble markers) to monitor: 1. longevity mechanisms in cognitive health; 2. early, preclinical diagnosis of neurodegenerative diseases that cause cognitive disorders; 3. therapy success; 4. the improvement of the complex clinical management of the affected people and therefore to improve the significant social, welfare and economic that these pathologies bring to society.5. aging trajectories and their association with mortality and neurodegenerative diseases.
Brief description of the activities and of the intermediate results: Partner UNIPD team continued its collection and analysis of key biomarkers— NfL, GFAP, and pTau181—in the Parkinson’s disease (PD) population. These plasma/serum biomarkers, identified jointly with the other partner (UNIFI), are deemed highly relevant in the neurodegenerative context. Partner UNIPD has conducted serum analyses for NfL, GFAP, and pTau181 in 92 PD patients, along with 20 age-, education-, and sex-matched healthy controls (HC). Additionally, a subgroup of PD patients (n=65) underwent a comprehensive neuropsychological assessment, with 44 categorized as PD with normal cognition (PD-NC) and 21 with mild cognitive deficits (PD-MCI). Biomarker concentrations were measured using commercially available Simoa kits. Their preliminary findings indicate higher levels of neurodegeneration biomarkers in PD compared to HC, with NfL and GFAP potentially serving as indicators for distinguishing PD patients with MCI. Specifically, elevated NfL levels were associated with poorer performance in the attentional domain. By contrast, the role of pTau181 in PD and its relationship with cognition require further elucidation. These initial results will be presented orally at the national congress "10th Congress of the Italian Parkinson's Disease and Movement Disorders Society/LIMPE-DISMOV."
Furthermore, UNIPD conducted preliminary analyses in a subgroup of PD patients who underwent MRI and an extensive neuropsychological assessment. The main aim was to explore cortical and subcortical differences between PD patients with vs. without cognitive deficits (n=14 PD vs 34, respectively) and their association with neurodegenerative biomarkers (NfL, GFAP, pTau181). Although these results are highly preliminary (p<0.05, without FDR/FEW correction), they observed significant involvement of numerous subcortical regions. The sample size needs to be expanded to potentially identify stronger differences, given the substantial variability between the two PD-subgroups.
Partner UNIFI (Prof Nacmias) has studied the usefulness of GFAP, NfL and pTau 181 for the early detection of dementia before the onset of clinical stages. The results are reported in a recently accepted paper (Ingannato et al., in press).
Research products of the reported period related to this Task:
Main policy, industrial and scientific implications: Data Analysis and drafting article on the role of HL in the dyad caregiver/older person
Partner UNIPD has expanded the numerosity for the preliminary analyses in PD patient sample to explore the relation between biofluid biomarkers (NFl, GFAP, pTau181) and brain imaging (structural MRI). New results are expected by the end of the October. A paper titled “The role of cerebellum in physical and functional impairment of older adults with mild cognitive impairment” has been submitted.
In the framework of task 3.2, UNIPD focused on three subtasks involving the analysis, data interpretation and writing of the following works:
1) The role of serum biomarkers in Parkinsonian disorders, Alzheimer’s disease and Frontotemporal dementia. In this study, we analyzed and discussed the role of GFAP, NfL, and pTau181 in a cohort of 179 participants, comprising: 120 Parkinson’s disease (PD) patients, 88 with Alzheimer’s disease (AD), 16 with Frontotemporal dementia (FTD), 11 with multiple system atrophy (MSA) and 14 with progressive supranuclear palsy (PSP) patients. We compared them with 30 sex and age-matched healthy individuals (HC). The serum biomarkers were analyzed with the SIMOA technique.
2) Serum GFAP and NFL Correlates of Brain Morphometry and Cognitive Dysfunction in Parkinson's Disease. This work examined the relationship between blood biomarkers, brain volumes, and cognitive state in a cohort of 58 PD patients. Patients were stratified in 37 PD with no cognitive impairment (PD-NC) and 21 PD with cognitive impairment (PD-CI), for each patient one T1-weighted and one T2-weighted FLAIR image was acquired on a Philps 3T scanner. The serum biomarkers were analyzed with the SIMOA technique. Key findings revealed that the GFAP-NFL ratio showed the largest and most widespread inverse correlations with brain volumes, particularly in the anterior cingulate region. These correlations remained significant after adjusting for age, gender, intracranial volume, and education. Additionally, brain volume differences between PD-NC and PD-CI groups were significant.
3) Plasma pTau217 as a Marker for Alzheimer’s Co-Pathology in Parkinson’s Spectrum Disorders. Here, we evaluate the utility of plasma pTau217 for detecting AD co-pathology in parkinsonian disorders and its association with cognitive impairment. The PADUA-CESNE cohort included 170 participants: 57 with PD, 4 with dementia with Lewy bodies (DLB), 28 with PSP, 4 with corticobasal syndrome (CBS) patients, 51 HC and 26 with mild cognitive deficits (MCI). Plasma pTau217 was measured using a research-use-only Lumipulse G1200 assay (Fujirebio, Japan). We found that pTau217 is elevated in PD patients with cognitive impairment, particularly PDD/DLB, but not in cognitively normal PD. It may serve as a reliable marker of AD co-pathology, warranting further validation with PET imaging.
During this trimester, UNIPD promoted a third mission activity as part of the SOPRANO dissemination project. Two events were organized to promote healthy aging: “Orchestra Asclepio in Concerto – Quando la musica diventa cura”. “La musica del cervello”.
Additionally, a poster was presented at the Autumn Meeting of the SINP (Bologna, December 13, 2024). The poster, titled “Optimal MMSE and MoCA Cutoffs for Cognitive Diagnoses in Parkinson’s Disease: A Data-Driven Decision Tree Model,” showcased our latest findings on cognitive diagnostic thresholds in PD.
Devita, M., Debiasi, G., … Cauzzo, S, … Anglani, M. et al. The Role of Cognitive Reserve in Protecting Cerebellar Volumes of Older Adults with mild Cognitive Impairment. Cerebellum 23, 1966–1974 (2024). https://doi.org/10.1007/s12311-024-01695-w