Systematic Appraisal Using Immunohistochemistry of Brain Pathology in Aged and Demented Subjects

<i>Background/Aims: </i>Abnormal processing of hyperphosphorylated τ (HPτ), amyloid-β (Aβ) and α-synuclein (αS) proteins is considered as causative with regard to the clinical symptoms in age-related neurodegenerative diseases. <i>Methods: </i>In this retrospective, postmortem study applying immunohistochemical methodology, we assessed Alzheimer’s-disease (AD)-related HPτ and Aβ pathology in 178 subjects with αS pathology. <i>Results: </i>These pathologies were frequently seen concomitantly, i.e. HPτ in 83% and Aβ in 62% of the αS-positive cases. Furthermore, the striatum was frequently involved, particularly in subjects with cognitive impairment (65%). The predictive value of widespread HPτ 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 αS pathology, i.e. stages 5–6 according to Braak’s Parkinson disease staging, was debatable. Fifty-three percent of the subjects with widespread αS pathology and no or mild AD-related HPτ pathology were cognitively unimpaired. It is noteworthy that striatal Aβ pathology was more often seen in demented subjects independently of HPτ and/or αS status. <i>Conclusion:</i> The causative pathology in subjects with clinically diagnosed dementia with Lewy bodies needs to be clarified in future studies.