Significant Overlap of α-Synuclein, Amyloid-β, and Phospho-Tau Pathologies in Neuropathological Diagnosis of Lewy-related Pathology: Evidence from China Human Brain Bank

Abstract

Background: Lewy-related pathology (LRP), primarily comprised of α-synuclein, is a typical neuropathological change that has been identified in many neurodegenerative disorders such as Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies.

Objective: To investigate the distribution of LRP in the China Human Brain Bank, the co-occurrence of neuropathologic features of Alzheimer's disease (AD) in LRP cases, and LRP-related cognitive dysfunction.

Methods: LRP neuropathological diagnosis was performed in 180 postmortem brains. AD neuropathological diagnosis was then performed in the 21 neuropathologically-diagnosed LRP cases. Antemortem cognitive functioning evaluation (Everyday Cognitive, ECog) was assessed for brain donors by the immediate kin of the donor within 24 hours after death.

Results: 12% (21 in 180) postmortem brains were neuropathologically diagnosed as LRP cases. 86% (18 in 21) aged above 80, 81% (17 in 21) LRP cases combined with AD neuropathology, and 62% (13 in 21) combined with both the intermediate or high-level amyloid-β and phospho-tau pathologies. ECog scores showed significant differences between the groups of LRP brainstem-predominant type and LRP diffuse neocortical type, and between groups of AD and the combined LRP (diffuse neocortical type)-AD.

Conclusion: The overlap of neocortical α-synuclein, amyloid-β, phospho-tau, and neuritic plaques in LRP suggested the potential interplay among the common characteristics of proteinopathies in the late stage of neuropathological development of LRP in human brains. The anatomic progression of LRP, the process of α-synuclein spreading from the brainstem to limbic and neocortical regions, might aggravate the deterioration of cognitive function in addition to that effect of AD.

Keywords: Alzheimer’s disease; Everyday Cognitive (ECog); LRP-AD neuropathology; Lewy-related pathology; amyloid-β; phospho-tau; α-synuclein.