The limbic and neocortical contribution of α-synuclein, tau, and amyloid β to disease duration in dementia with Lewy bodies

Introduction: We sought to assess the individual and combined contribution of limbic and neocortical alpha-synuclein, tau, and amyloid beta (A beta) to duration of illness in dementia with Lewy bodies (DLB). Methods: Quantitative digital pathology of limbic and neocortical alpha-synuclein, tau, and A beta was assessed in 49 patients with clinically probable DLB. Regression modeling examined the unique and shared contribution of each pathology to the variance of illness duration. Results: Patients with diffuse Lewy body disease had more severe pathology of each type and a shorter duration of illness than individuals with transitional Lewy body disease. The three pathologies accounted for 25% of the total variance of duration of illness, with 19% accounted for by alpha-synuclein alone or in combination with tau and A beta. When the diffuse Lewy body disease group was examined separately, alpha-synuclein deposition significantly exceeded that of tau and A beta. In this model, 20% of 24% total variance in the model for duration of illness was accounted for independently by alpha-synuclein. Discussion: In DLB, alpha-synuclein is an important predictor of disease duration, both independently and synergistically with tau and A beta. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.