α-Synuclein Seed Amplification in CSF and Brain from Patients with Different Brain Distributions of Pathological α-Synuclein in the Context of Co-Pathology and Non-LBD Diagnoses

被引：51

作者：

Arnold, Moriah R. ^{[1
]}

Coughlin, David G. ^{[2
]}

Brumbach, Barbara H. ^{[3
]}

Smirnov, Denis S. ^{[2
]}

Concha-Marambio, Luis ^{[4
]}

Farris, Carly M. ^{[4
]}

Ma, Yihua ^{[4
]}

Kim, Yongya ^{[2
]}

Wilson, Edward N. ^{[5
]}

Kaye, Jeffrey A. ^{[6
]}

Hiniker, Annie ^{[7
]}

Woltjer, Randy L. ^{[8
]}

Galasko, Doug R. ^{[2
]}

Quinn, Joseph F. ^{[6
,9
]}

机构：

[1] Oregon Hlth & Sci Univ, Med Scientist Training Program, Portland, OR 97239 USA

[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[3] Oregon Hlth & Sci Univ, Biostat & Design Program, Portland, OR 97239 USA

[4] Amprion Inc, San Francisco, CA USA

[5] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[6] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA

[7] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[8] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA

[9] Portland Virginia Med Ctr, Parkinsons Dis Res Educ & Clin Care Ctr PADRECC, Portland, OR USA

来源：

ANNALS OF NEUROLOGY | 2022年 / 92卷 / 04期

基金：

美国国家卫生研究院;

关键词：

FRONTOTEMPORAL LOBAR DEGENERATION; LEWY BODY PATHOLOGY; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; NEUROPATHOLOGIC ASSESSMENT; SEX-DIFFERENCES; DEMENTIA; BODIES; CONSORTIUM; CONSENSUS;

D O I：

10.1002/ana.26453

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective The purpose of this study was to determine the sensitivity and specificity of alpha-synuclein seed amplification assay (alpha Syn-SAA) in antemortem and postmortem cerebrospinal fluid (CSF) of autopsy-confirmed patients with different distributions of pathological alpha Syn, co-pathologies, and clinical diagnoses. Methods The alpha Syn-SAA was used to test antemortem CSF samples from 119 subjects with a variety of clinical syndromes and standardized neuropathological examinations from Oregon Health and Science University (OHSU) and University of California San Diego (UCSD; 56 additional postmortem CSF samples available). The alpha Syn-SAA was also applied to frontal cortex and amygdala homogenates. Sensitivity and specificity were compared across distributions of alpha Syn pathology. Clinical data and co-pathologies were compared across alpha Syn-SAA positive and negative groups. Results Fifty-three individuals without and 66 with alpha Syn-pathology (neocortical [n = 38], limbic [n = 7], and amygdala-predominant [n = 21]) were included. There was a sensitivity of 97.8% and specificity of 98.1% of the alpha Syn-SAA to identify patients with limbic/neocortical pathology from antemortem CSF. Sensitivity to detect amygdala-predominant pathology was only 14.3%. Postmortem CSF and brain tissue alpha Syn-SAA analyses also showed higher assay positivity in samples from limbic/neocortical cases. Interpretation CSF alpha Syn-SAA reliably identifies alpha Syn seeds in patients with diffuse alpha Syn pathology in the context of co-pathology and non-Lewy body disease (LBD) diagnoses. The analysis of brain homogenates suggests that pathological alpha Syn in the amygdala might differ from pathological alpha Syn in the frontal cortex. The alpha Syn-SAA might facilitate the differential diagnosis of dementias with mixed pathologies. ANN NEUROL 2022

引用

页码：650 / 662

页数：13

共 50 条

[1] Low clinical diagnostic accuracy of early vs advanced Parkinson disease Clinicopathologic study [J].

Adler, Charles H. ;

Beach, Thomas G. ;

Hentz, Joseph G. ;

Shill, Holly A. ;

Caviness, John N. ;

Driver-Dunckley, Erika ;

Sabbagh, Marwan N. ;

Sue, Lucia I. ;

Jacobson, Sandra A. ;

Belden, Christine M. ;

Dugger, Brittany N. .

NEUROLOGY, 2014, 83 (05) :406-412

[2]

Baba M, 1998, AM J PATHOL, V152, P879

[3] Nigral pathology and parkinsonian signs in elders without Parkinson disease [J].

Buchman, Aron S. ;

Shulman, Joshua M. ;

Nag, Sukriti ;

Leurgans, Sue E. ;

Arnold, Steven E. ;

Morris, Martha C. ;

Schneider, Julie A. ;

Bennett, David A. .

ANNALS OF NEUROLOGY, 2012, 71 (02) :258-266

[4] Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration [J].

Cairns, Nigel J. ;

Bigio, Eileen H. ;

Mackenzie, Ian R. A. ;

Neumann, Manuela ;

Lee, Virginia M. -Y. ;

Hatanpaa, Kimmo J. ;

White, Charles L., III ;

Schneider, Julie A. ;

Grinberg, Lea Tenenholz ;

Halliday, Glenda ;

Duyckaerts, Charles ;

Lowe, James S. ;

Holm, Ida E. ;

Tolnay, Markus ;

Okamoto, Koichi ;

Yokoo, Hideaki ;

Murayama, Shigeo ;

Woulfe, John ;

Munoz, David G. ;

Dickson, Dennis W. ;

Ince, Paul G. ;

Trojanowski, John Q. ;

Mann, David M. A. .

ACTA NEUROPATHOLOGICA, 2007, 114 (01) :5-22

[5] Sex differences in Parkinson's disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics [J].

Camilo Jurado-Coronel, Juan ;

Cabezas, Ricardo ;

Avila Rodriguez, Marco Fidel ;

Echeverria, Valentina ;

Miguel Garcia-Segura, Luis ;

Barreto, George E. .

FRONTIERS IN NEUROENDOCRINOLOGY, 2018, 50 :18-30

[6] Clinical Features of Alzheimer Disease With and Without Lewy Bodies [J].

Chung, Eun Joo ;

Babulal, Ganesh M. ;

Monsell, Sarah E. ;

Cairns, Nigel J. ;

Roe, Catherine M. ;

Morris, John C. .

JAMA NEUROLOGY, 2015, 72 (07) :789-796

[7] Seed Amplification Assay to Diagnose Early Parkinson's and Predict Dopaminergic Deficit Progression [J].

Concha-Marambio, Luis ;

Farris, Carly M. ;

Holguin, Bret ;

Ma, Yihua ;

Seibyl, John ;

Russo, Marco J. ;

Kang, Un J. ;

Hutten, Samantha J. ;

Merchant, Kalpana ;

Shahnawaz, Mohammad ;

Soto, Claudio .

MOVEMENT DISORDERS, 2021, 36 (10) :2444-2446

[8] Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders [J].

Coughlin, David ;

Xie, Sharon X. ;

Liang, Mendy ;

Williams, Andrew ;

Peterson, Claire ;

Weintraub, Daniel ;

McMillan, Corey T. ;

Wolk, David A. ;

Akhtar, Rizwan S. ;

Hurtig, Howard I. ;

Coslett, H. Branch ;

Hamilton, Roy H. ;

Siderowf, Andrew D. ;

Duda, John E. ;

Rascovsky, Katya ;

Lee, Edward B. ;

Lee, Virginia M. -Y. ;

Grossman, Murray ;

Trojanowski, John Q. ;

Irwin, David J. .

ANNALS OF NEUROLOGY, 2019, 85 (02) :259-271

[9] Multimodal in vivo and postmortem assessments of tau in Lewy body disorders [J].

Coughlin, David G. ;

Phillips, Jeffrey S. ;

Roll, Emily ;

Peterson, Claire ;

Lobrovich, Rebecca ;

Rascovsky, Katya ;

Ungrady, Molly ;

Wolk, David A. ;

Das, Sandhitsu ;

Weintraub, Daniel ;

Lee, Edward B. ;

Trojanowski, John Q. ;

Shaw, Leslie M. ;

Vaishnavi, Sanjeev ;

Siderowf, Andrew ;

Nasrallah, Ilya M. ;

Irwin, David J. ;

McMillan, Corey T. .

NEUROBIOLOGY OF AGING, 2020, 96 :137-147

[10] Novel conformation-selective alpha-synuclein antibodies raised against different in vitro fibril forms show distinct patterns of Lewy pathology in Parkinson's disease [J].

Covell, D. J. ;

Robinson, J. L. ;

Akhtar, R. S. ;

Grossman, M. ;

Weintraub, D. ;

Bucklin, H. M. ;

Pitkin, R. M. ;

Riddle, D. ;

Yousef, A. ;

Trojanowski, J. Q. ;

Lee, V. M. -Y. .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2017, 43 (07) :604-620

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