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. 2018 Mar;14(3):330-339.
doi: 10.1016/j.jalz.2017.09.014. Epub 2017 Oct 31.

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

Tanis J Ferman  1 , Naoya Aoki  2 , Julia E Crook  3 , Melissa E Murray  4 , Neill R Graff-Radford  5 , Jay A van Gerpen  5 , Ryan J Uitti  5 , Zbigniew K Wszolek  5 , Jonathan Graff-Radford  6 , Otto Pedraza  7 , Kejal Kantarci  8 , Bradley F Boeve  6 , Dennis W Dickson  4
Affiliations

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

Tanis J Ferman et al. Alzheimers Dement. 2018 Mar.

Abstract

Introduction: We sought to assess the individual and combined contribution of limbic and neocortical α-synuclein, tau, and amyloid β (Aβ) to duration of illness in dementia with Lewy bodies (DLB).

Methods: Quantitative digital pathology of limbic and neocortical α-synuclein, tau, and Aβ 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 α-synuclein alone or in combination with tau and Aβ. When the diffuse Lewy body disease group was examined separately, α-synuclein deposition significantly exceeded that of tau and Aβ. In this model, 20% of 24% total variance in the model for duration of illness was accounted for independently by α-synuclein.

Discussion: In DLB, α-synuclein is an important predictor of disease duration, both independently and synergistically with tau and Aβ.

Keywords: Alzheimer's disease; Commonality analysis; Lewy body; Parkinsonism; Pathology; REM sleep behavior disorder.

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Conflict of interest statement

Potential Conflicts of Interest:

Drs. Ferman, Aoki, Kantarci, Van Gerpen, J. Graff-Radford, Pedraza, Murray and Dickson report no conflicts of interest.

Dr. Boeve has served as an investigator for clinical trials sponsored by GE Healthcare, FORUM Pharmaceuticals and C2N Diagnostics. He receives royalties from the publication of a book entitled Behavioral Neurology of Dementia (Cambridge Medicine, 2009). He serves on the Scientific Advisory Board of the Tau Consortium.

Dr. N. Graff-Radford serves on a scientific advisory board for Codman; serves on the editorial boards of The Neurologist and Alzheimer Disease and Therapy; has received publishing royalties from UpToDate, Inc.; and receives research support from Biogen, Lilly and Axovant. He has consulted for Cytox.

Dr. Wszolek is supported by The Cecilia and Dan Carmichael Family Foundation and James C. and Sarah K. Kennedy Fund, and The Sol Goldman Charitable Trust.

Dr. Uitti serves as an Associate Editor for Neurology,® receives research funding from Boston Scientific.

Figures

Fig. 1
Fig. 1. Digital Pathology for α-synuclein, tau and β-amyloid
Image analysis for α-synuclein, β-amyloid and tau. Panels on the left indicate immunohistochemistry for each antibody and panels on the right represent the digital scans of the images used for pixel count algorithms resulting in a percentage burden reflecting the amount of stained pathology in the area examined.
Fig. 2
Fig. 2
Regional distribution of the pathologies. Parahipp = parahippocampal gyrus, Cingulate = cingulate gyrus, Frontal = middle frontal gyrus, Parietal = inferior parietal gyrus, Inf. Temp = inferior temporal gyrus, Occ. Temp = Occipitotemporal gyrus, Occipital = Visual Association Cortex.
Fig. 3
Fig. 3. Mean burden of limbic and cortical pathology
Regression commonality analysis for the TLBD and DLBD group and for DLBD-only group. Values represent the unique and shared variance accounted for by each pathology type for duration of illness.
Fig. 4
Fig. 4
Commonality analysis
See this image and copyright information in PMC

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