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

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). Quantitative digital pathology of limbic and neocortical α-synuclein, tau, and Aβ was assessed in 49 patients with cl...

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Published in:Alzheimer's & dementia 2018-03, Vol.14 (3), p.330-339
Main Authors: Ferman, Tanis J., Aoki, Naoya, Crook, Julia E., Murray, Melissa E., Graff-Radford, Neill R., van Gerpen, Jay A., Uitti, Ryan J., Wszolek, Zbigniew K., Graff-Radford, Jonathan, Pedraza, Otto, Kantarci, Kejal, Boeve, Bradley F., Dickson, Dennis W.
Format: Article
Language:English
Subjects:
Aged
alpha-Synuclein - metabolism
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Commonality analysis
Disease Progression
Female
Humans
Lewy body
Lewy Body Disease - metabolism
Lewy Body Disease - pathology
Limbic System - metabolism
Limbic System - pathology
Male
Neocortex - metabolism
Neocortex - pathology
Parkinsonism
Pathology
Prospective Studies
REM sleep behavior disorder
tau Proteins - metabolism
Time Factors
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Summary: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). 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. 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. In DLB, α-synuclein is an important predictor of disease duration, both independently and synergistically with tau and Aβ.
ISSN:1552-5260
1552-5279
DOI:10.1016/j.jalz.2017.09.014