@article{9e7e54ffec964fde89da6fdecad27437,
title = "CSF tau and β-amyloid predict cerebral synucleinopathy in autopsied Lewy body disorders",
abstract = "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 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 181, and Aβ 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 Aβ 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 Aβ 1-42 (R 2 = 0.43-0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF Aβ 1-42 (R 2 = 0.31, p < 0.001) and higher CSF t-tau/Aβ 1-42 ratio (R 2 = 0.27, p = 0.01). CSF t-tau/Aβ 1-42 ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF Aβ 1-42 had 77% specificity and 82% sensitivity for neocortical SYN stage. Conclusions Higher antemortem CSF t-tau/Aβ 1-42 and lower Aβ 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.",
author = "Irwin, {David J.} and Xie, {Sharon X.} and David Coughlin and Naomi Nevler and Akhtar, {Rizwan S.} and McMillan, {Corey T.} and Lee, {Edward B.} and Wolk, {David A.} and Daniel Weintraub and Alice Chen-Plotkin and Duda, {John E.} and Meredith Spindler and Andrew Siderowf and Hurtig, {Howard I.} and Shaw, {Leslie M.} and Murray Grossman and Trojanowski, {John Q.}",
note = "Funding Information: This study was funded by the NIH. Some authors report receiving funding from various government agencies, foundations, and pharmaceutical companies. Dr. Xie and Dr. Weintraub report receiving consultancy fees from various pharmaceutical companies. Dr. Weintraub reports receiving royalties and legal consultation fees. Dr. Wolk received grant funding from Merck, Biogen, Avid Radiopharmaceuticals and Eli Lilly and personal fees from GE Healthcare, Merck, and Janssen. Go to Neurology.org/N for full disclosures. Funding Information: Funding provided by the National Institute on Aging (AG010124), National Institute of Neurological Disorders and Stroke (NS088341, NS053488), and National Center for Advancing Translational Sciences of the NIH under award TL1TR001880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: D. Irwin reports travel stipend for academic research meeting from GE Healthcare. S. Xie receives research funding from US NIH and serves as a consultant to Roche on 2 cancer clinical trials. D. Coughlin, N. Nevler, R. Akhtar, C. McMillan, and E. Lee, report no disclosures relevant to the manuscript. D. Wolk received grant funding from Merck, Biogen, Avid Radiopharmaceuticals and Eli Lilly and personal fees from GE Healthcare, Merck, and Janssen. D. Weintraub has received research funding or support from Michael J. Fox Foundation for Parkinson{\textquoteright}s Research, NIH (National Institute for Neurological Disorders and Stroke), Novartis Pharmaceuticals, Department of Veterans Affairs, Avid Radiopharmaceuticals, Alzheimer{\textquoteright}s Disease Cooperative Study, and International Parkinson and Movement Disorder Society; honoraria for consultancy from Acadia, Biogen, Biotie (Acorda), Bracket, Clintrex LLC, Eisai Inc, Eli Lilly, Lundbeck, Takeda, UCB, and the CHDI Foundation; license fee payments from the University of Pennsylvania for QUIP and QUIP-RS; royalties from Wolters Kluwer; and fees for legal consultation for lawsuits related to medication prescribing in patients with PD. A. Chen-Plotkin reports no disclosures relevant to the manuscript. J. Duda has received research funding or support from Michael J. Fox Foundation for Parkinson{\textquoteright}s Research, NIH, and Department of Veterans Affairs. M. Spindler, A. Siderowf, H. Hurtig, L. Shaw, M. Grossman, and J. Trojanowski report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures. Publisher Copyright: {\textcopyright} 2018 American Academy of Neurology.",
year = "2018",
month = mar,
day = "20",
doi = "10.1212/WNL.0000000000005166",
language = "English (US)",
volume = "90",
pages = "e1038--e1046",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "12",
}