Neurodegenerative disorders are often associated with cellular dysfunction caused by underlying pro-tein-misfolding signalling. Numerous neuropathologies are diagnosed at late stage symptomatic changes which occur in response to these molecular malfunctions and treatment is often too late or restricted only to the slowing of further cell death. Important new strategies to identify early biomarkers with predictive value to intervene with disease progression at stages where cell dysfunction has not progressed irreversibly is of paramount importance. Thus, the identification of these markers presents an essential opportunity to identify and target disease pathways. This review highlights some important metabolic alterations detected in neurodegeneration caused by misfolded prion protein and discusses common toxicity pathways iden-tified across different neurodegenerative diseases. Thus, having established some commonalities between various degenerative conditions, detectable metabolic changes may be of extreme value as an early diag-nostic biomarker in disease.