Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects

Background/ Aims: Abnormal processing of hyperphosphorylated tau (HP tau), amyloid-beta (A beta) and alpha-synuclein (alpha S) proteins is considered as causative with regard to the clinical symptoms in age-related neurodegenerative diseases. Methods: In this retrospective, postmortem study applying immunohistochemical methodology, we assessed Alzheimer's-disease ( AD)- related HP tau and A beta pathology in 178 subjects with alpha S pathology. Results: These pathologies were frequently seen concomitantly, i. e. HP tau in 83% and A beta in 62% of the alpha S- positive cases. Furthermore, the striatum was frequently involved, particularly in subjects with cognitive impairment ( 65%). The predictive value of widespread HP tau pathology, i. e. stages V - VI, with respect to cognitive impairment was high, since all 18 subjects presenting with this stage were demented. In contrast, the predictive value of widespread alpha S pathology, i. e. stages 5 - 6 according to Braak's Parkinson disease staging, was debatable. Fifty-three percent of the subjects with widespread alpha S pathology and no or mild AD-related HP tau pathology were cognitively unimpaired. It is noteworthy that striatal A beta pathology was more often seen in demented subjects independently of HP tau and/ or alpha S status. Conclusion: The causative pathology in subjects with clinically diagnosed dementia with Lewy bodies needs to be clarified in future studies. Copyright (c) 2008 S. Karger AG, Basel.