Regional Overlap of Pathologies in Lewy Body Disorders

Abstract

Lewy body disorders (LBD) are common neurodegenerative diseases characterized by the presence of aggregated α-synuclein in Lewy bodies and Lewy neurites in the central and peripheral nervous systems. The brains of patients with LBD often display other comorbid pathologies, i.e. insoluble tau, β-amyloid aggregates, TAR DNA-binding protein 43 (TDP-43) deposits, and argyrophilic grain disease (AGD). The incidence and physiological relevance of these concurrent pathological findings remain controversial. We performed a semiquantitative detailed mapping of α-synuclein, tau, β-amyloid (Aβ), TDP-43, and AGD pathologies in 17 areas in 63 LBD cases (44 with Parkinson disease [PD], 28 with dementia, and 19 with dementia with Lewy bodies). APOE and MAPT genetic variants were also investigated. A majority of LBD cases had 2 or 3 concomitant findings, particularly Alzheimer disease-related pathology. Pathological stages of tau, β-amyloid and α-synuclein pathologies were increased in cases with dementia. Aβ score was the best correlate of the time to dementia in PD. In addition, β-amyloid deposition correlated with α-synuclein load in all groups. MAPT H1 haplotype did not influence any assessed pathology in PD. These results highlight the common concurrence of pathologies in patients with LBD that may have an impact on the clinical expression of the diseases.

Keywords: Copathology; Dementia with Lewy bodies; Parkinson disease; Parkinson disease dementia; Tau; α-Synuclein; β-Amyloid.