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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid beta-Peptides / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Lewy Body Disease / metabolism*
  • Lewy Body Disease / pathology
  • Limbic System / metabolism*
  • Limbic System / pathology
  • Male
  • Neocortex / metabolism*
  • Neocortex / pathology
  • Prospective Studies
  • Time Factors
  • alpha-Synuclein / metabolism*
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • MAPT protein, human
  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins