CSF tau and amyloid-beta predict cerebral synucleinopathy in autopsied Lewy body disorders.
NEUROLOGY(2018)
摘要
Objective To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). Methods 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 a-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN -AD = 14). Ordinal pathology scores for tau, beta-amyloid (A beta), 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(181), and A beta(1-42) 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. Results SYN + AD had higher CSF t-tau (mean difference 27.0 +/- 8.6 pg/mL) and lower A beta(1-42) (mean difference -84.0 +/- 22.9 g/mL) compared to SYN -AD (p < 0.01, both). Increasing global cerebral tau and plaque scores were associated with higher CSF t-tau (R-2 = 0.15-0.16, p < 0.05, both) and lower A beta(1-42) (R-2 = 0.43-0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF A beta(1-42) (R-2 = 0.31, p < 0.001) and higher CSF t-tau/A beta(1-42) ratio (R-2 = 0.27, p = 0.01). CSF t-tau/A beta(1-42) ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF A beta(1-42) had 77% specificity and 82% sensitivity for neocortical SYN stage. Conclusions Higher antemortem CSF t-tau/A beta(1-42) and lower A beta(1-42) 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.
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