CSF tau and β-amyloid predict cerebral synucleinopathy in autopsied Lewy body disorders.
retrospective_cohort · Level III
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- Also identified by DOI 10.1212/WNL.0000000000005166 and PMC identifier 5874449.
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Abstract
To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology. CSF total tau (t-tau), phosphorylated tau at threonine<sub>181</sub>, and Aβ<sub>1-42</sub> levels were compared between LBD and control groups and correlated with global cerebral pathology scores in LBD with linear regression. Diagnostic accuracy for postmortem categorization of LBD into SYN + AD vs SYN - AD or neocortical vs brainstem/limbic SYN stage was tested with receiver operating curves. SYN + AD had higher CSF t-tau (mean difference 27.0 ± 8.6 pg/mL) and lower Aβ<sub>1-42</sub> (mean difference -84.0 ± 22.9 g/mL) compared to SYN - AD (<i>p</i> < 0.01, both). Increasing global cerebral tau and plaque scores were associated with higher CSF t-tau (<i>R</i><sup>2</sup> = 0.15-0.16, <i>p</i> < 0.05, both) and lower Aβ<sub>1-42</sub> (<i>R</i><sup>2</sup> = 0.43-0.49, <i>p</i> < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF Aβ<sub>1-42</sub> (<i>R</i><sup>2</sup> = 0.31, <i>p</i> < 0.001) and higher CSF t-tau/Aβ<sub>1-42</sub> ratio (<i>R</i><sup>2</sup> = 0.27, <i>p</i> = 0.01). CSF t-tau/Aβ<sub>1-42</sub> ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF Aβ<sub>1-42</sub> had 77% specificity and 82% sensitivity for neocortical SYN stage. Higher antemortem CSF t-tau/Aβ<sub>1-42</sub> and lower Aβ<sub>1-42</sub> levels are predictive of increasing cerebral AD and SYN pathology. These biomarkers may identify patients with LBD vulnerable to cortical SYN pathology who may benefit from both SYN and AD-targeted disease-modifying therapies.
Medical subject headings
- Amyloid beta-Peptides
- Brain
- Lewy Body Disease
- Peptide Fragments
- alpha-Synuclein
- tau Proteins