Introduction: Human
prion diseases are a heterogeneous group of incurable and debilitating conditions characterized by a progressive degeneration of the central nervous system. The conformational changes of the cellular
prion protein and its formation into an abnormal
isoform, spongiform degeneration, neuronal loss, and
neuroinflammation are central to
prion disease pathogenesis. It has been postulated that truncated variants of aggregation-prone
proteins are implicated in neurodegenerative mechanisms. An increasing body of evidence indicates that proteolytic fragments and truncated variants of the
prion protein are formed and accumulated in the brain of
prion disease patients. These
prion protein variants provide a high degree of relevance to disease pathology and diagnosis. Areas covered: In the present review, we summarize the current knowledge on the occurrence of truncated
prion protein species and their potential roles in pathophysiological states during
prion diseases progression. In addition, we discuss their usability as a diagnostic
biomarker in
prion diseases. Expert opinion: Either as a primary factor in the formation of
prion diseases or as a consequence from neuropathological affection, abnormal
prion protein variants and fragments may provide independent information about mechanisms of
prion conversion, pathological states, or
disease progression.