Widespread axonal damage in the brain of drug abusers as evidenced by accumulation of β‐amyloid precursor protein (β‐APP): an immunohistochemical investigation

Background  In drug abusers, white matter changes have been described by neuroimaging analyses in different brain regions. A specific pattern of involvement or a predominance of a specific brain region could not be drawn. Aims  To examine alterations of the white matter as a possible morphological substrate of the neuroimaging findings. Methods  Brain specimens of 30 polydrug abusers and 20 controls were obtained at autopsy. The white matter from 11 different brain regions was analysed by means of immunohistochemistry for β‐amyloid precursor protein (β‐APP), a marker of axonal damage. Findings  In the white matter of polydrug abusers, β‐APP‐immunopositive accumulations were increased significantly compared to controls. They were more prominent in the brains of younger drug abusers than in those of the elderly. With the exception of five cases (four polydrug abusers and one control case), there were no significant white matter changes seen on myelin‐stained sections, but there was a concomitant microglial activation. Conclusions  Our results show a significant axonal damage in the brains of polydrug abusers, which might represent the morphological substrate of a chronic‐progressive drug‐induced toxic‐metabolic process. It is yet to be established if the observed changes are responsible for the alterations seen in different neuroimaging analyses and which drugs of abuse might be of major pathogenetic significance.