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European Pharmaceutical Students’ Association
PLEIOTROPHIN AND MIDKINE AS BIOMARKERS AND POSSIBLE DRUG TARGETS IN DEMENTIAS Author: Sara Martín Martínez. Scientific Coordinators: Gonzalo Herradón Gil-Gallardo, Marta del Campo Milán. Institution: University CEU-San Pablo (Madrid, Spain).
INTRODUCTION: Pleiotrophin (PTN) and Midkine (MK) constitute a small family of heparin binding factors, with overlapping diverse functions in the maintenance of the central nervous system (CNS). Recent studies highlight the role of these cytokines in the modulation of neuroinflammatory processes on brain damage. Dysregulation of neuroinflammatory mechanisms play a relevant role in the development of different neurodegenerative dementias. AIM: In this project we aimed to study the relation between these cytokines and different dementia types (Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Lewy Bodies Dementia (LBD)) through the neuroinflammatory response, using patients’ cerebrospinal fluid (CSF). MATERIALS AND METHODS: The concentration of PTN, MK and IL-6 was analyzed in CSF from non-demented controls (CON, n = 195), AD (n = 230), FTD (n = 199) and LBD (n = 123) patients using PEA-extension assay (Olink® Proteomics). Correlation of these proteins with the classical AD CSF biomarkers (β-amyloid 1-42 (Aβ142); total concentration of tau (t-Tau) and hyperphosphorylated tau (p-Tau)) and MiniMental State Examination (MMSE) test was also performed. RESULTS: CSF PTN was decreased in AD patients (p < 0.05) compared to controls and correlated with both t-Tau and p-Tau in AD. CSF MK was decreased in FTD patients compared to controls and AD (p < 0.05) and correlated with Aβ1-42 in LBD patients only and with Tau forms in AD and FTD patients. CSF IL-6 remained similar across the different diagnostic groups. PTN and MK levels inversely correlated in all the subjects, suggesting a possible interconnection between them on the development of dementia.
CONCLUSION: Our findings show the possibility that PTN and MK could be involved in specific types of dementias associated to neurodegeneration and neuroinflammation. PTN might be specially related to AD, where might be associated with the development of neurofibrillary tangles (NFTs). MK seems to be specially related to FTD and the development of tau aggregates in this dementia. These data suggest that PTN and MK are involved in the pathophysiology of AD and FTD respectively. Further studies are warranted to analyze their potential as novel targets for the development of therapeutic and/or diagnostic tools.
