β-amyloid precursor protein immunoreactivity in fatal polysubstance poisonings: a neuropathologically examined autopsy case series

It is not always possible to definitively establish fatal poisoning by means of postmortem toxicology alone. Beta-amyloid precursor protein (β-APP) immunoreactivity has been reported in substance poisoning deaths in various regions of the brain, opioids being of particular interest in this matter. We aimed to report β-APP immunoreactivity in polysubstance poisoning deaths, most of them buprenorphine-driven, and discuss the potential uses of β-APP in suspected fatal poisonings. We analysed a series of 14 neuropathologically examined medico-legal autopsy cases that had undergone toxicological analysis and systematic sampling of the brain for β-APP at the Finnish Institute for Health and Welfare. The cases comprised poisonings with vascular axonal injury (VAI) in β-APP (n = 7), poisonings without VAI in β-APP (n = 3), and controls (n = 4). All ten poisonings involved multiple substances. Eight were opioid-driven; other central nervous system (CNS) depressants and stimulants were also detected. β-APP immunoreactivity indicative of VAI was observed in seven cases; most common sites were the corpus callosum (n = 7), pons (n = 7), and internal capsule (n = 6). In conclusion, β-APP immunoreactivity was present in most poisoning deaths caused by CNS depressants. They may cause delayed death through respiratory depression, expediting the development of VAI that can be detected via β-APP. In such deaths, a good example being buprenorphine-driven ones, postmortem blood concentrations may not suffice to definitively establish poisoning.