Lysosomal trafficking markers covering PSAP, PGRN, SORT1 and LRP1 in body liquids and cerebral tissue as auxiliary indicative tool of traumatic brain injury.

Forensic science international 2026

Poniatowski ŁA, Siwińska A, Acewicz A, Kwiatkowska M, Olczak M

Abstract

Traumatic brain injury (TBI) constitutes the principal cause of disability and death globally. Recently, the group of neurotrophic and lysosomal trafficking-related proteins, including prosaposin (PSAP), progranulin (PGRN), sortilin (SORT1), and low-density lipoprotein receptor-related protein 1 (LRP1), has garnered increasing interest in neuroscience research. The aim of this study was to profile the post-mortem levels of PSAP, PGRN, SORT1 and LRP1, and to determine whether these biomarkers could serve as diagnostic tools for mechanistic stratification in forensic neuropathology and medico-legal investigations. The study involved a total of 40 cases, individuals with head injuries (n = 20) suspected to be the cause of death and control atraumatic cases of sudden death (n = 20) due to cardiopulmonary reasons. Serum and cerebrospinal fluid (CSF), were collected approximately 24 h post-mortem and analyzed through ELISA testing. Brain specimens were obtained during forensic autopsies and subjected to immunohistochemical staining. We observed the elevated concentration level of PSAP in CSF, and the elevated concentration level of PGRN within serum and CSF. In the frontal cortex, anti-SORT1 and anti-LRP1 immunostaining revealed a general homogenization of the reaction in the study group. The molecular and cellular evidence suggests lysosomal trafficking disruption as central element of fatal TBI. The redistribution of SORT1 and LRP1, together with CSF-specific PSAP elevation and systemic PGRN increase, support a model in which neuronal lysosomal stress, receptor trafficking breakdown, and systemic release of lysosomal proteins are intertwined. The potential use of PSAP, PGRN, SORT1, and LRP1 assays offers an novel tool for research regarding TBI diagnosis and pathogenesis.

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