Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads

被引：107

作者：

Salvado, Gemma ^{[1
]}

Ossenkoppele, Rik ^{[1
,2
,3
]}

Ashton, Nicholas J. ^{[4
,5
,6
,7
]}

Beach, Thomas G. ^{[8
]}

Serrano, Geidy E. ^{[8
]}

Reiman, Eric M. ^{[9
,10
]}

Zetterberg, Henrik ^{[11
,12
,13
,14
]}

Mattsson-Carlgren, Niklas ^{[1
,15
,16
]}

Janelidze, Shorena ^{[1
]}

Blennow, Kaj

Hansson, Oskar ^{[1
,17
]}

机构：

[1] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden

[2] Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Neurol, Amsterdam UMC Locat VUmc, Amsterdam, Netherlands

[3] Amsterdam Neurosci, Neurodegenerat, Amsterdam, Netherlands

[4] Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Gothenburg, Sweden

[5] Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Inst Clin Neurosci Inst, London, England

[6] NHS Fdn, NIHR Biomed Res Ctr Mental Hlth, London, England

[7] NHS Fdn, Biomed Res Unit Dementia South London & Maudsley, London, England

[8] Banner Sun Hlth Res Inst, Sun City, AZ USA

[9] Arizona State Univ, Banner Alzheimers Inst, Phoenix, AZ USA

[10] Univ Arizona, Phoenix, AZ USA

[11] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[12] UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England

[13] UCL, UK Dementia Res Inst, London, England

[14] Hong Kong Ctr Neurodegenerat Dis, Hong Kong, Peoples R China

[15] Skane Univ Hosp, Dept Neurol, Lund, Sweden

[16] Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden

[17] Skane Univ Hosp, Memory Clin, Malmo, Sweden

来源：

EMBO MOLECULAR MEDICINE | 2023年 / 15卷 / 05期

基金：

欧洲研究理事会; 瑞典研究理事会; 欧盟地平线“2020”;

关键词：

Alzheimer's disease; co-pathologies; head-to-head; neuropathology; p-tau species; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ARGYROPHILIC GRAINS; NEUROPATHOLOGIC ASSESSMENT; NEUROFILAMENT LIGHT; P-TAU; CSF; BRAIN; DEGENERATION; PREDICTION;

D O I：

10.15252/emmm.202217123

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To investigate and compare independent associations between multiple plasma biomarkers (p-tau181, p-tau217, p-tau231, A beta 42/40, GFAP, and NfL) and neuropathologic measures of amyloid and tau, we included 105 participants from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with antemortem plasma samples and a postmortem neuropathological exam, 48 of whom had longitudinal p-tau217 and p-tau181. When simultaneously including plaque and tangle loads, the A beta 42/40 ratio and p-tau231 were only associated with plaques (rho(A beta 42/40)[95%CI] = -0.53[-0.65, -0.35], rho(p-tau231)[95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (rho(GFAP)[95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (rho(p-tau217)[95%CI] = 0.40[0.21, 0.56], rho(p-tau181)[95%CI] = 0.36[0.15, 0.50]) and tangles (rho(p-tau217)[95%CI] = 0.52[0.34, 0.66]; rho(p-tau181)[95%CI] = 0.36[0.17, 0.52]). A model combining p-tau217 and the A beta 42/40 ratio showed the highest accuracy for predicting the presence of Alzheimer's disease neuropathological change (ADNC, AUC[95%CI] = 0.89[0.82, 0.96]) and plaque load (R-2 = 0.55), while p-tau217 alone was optimal for predicting tangle load (R-2 = 0.45). Our results suggest that high-performing assays of plasma p-tau217 and A beta 42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.

引用

页数：16

共 69 条

[1] TDP-43 deposition in prospectively followed, cognitively normal elderly individuals: correlation with argyrophilic grains but not other concomitant pathologies [J].

Arnold, Stacy J. ;

Dugger, Brittany N. ;

Beach, Thomas G. .

ACTA NEUROPATHOLOGICA, 2013, 126 (01) :51-57

[2] Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring [J].

Ashton, Nicholas J. ;

Janelidze, Shorena ;

Mattsson-Carlgren, Niklas ;

Binette, Alexa Pichet ;

Strandberg, Olof ;

Brum, Wagner S. ;

Karikari, Thomas K. ;

Gonzalez-Ortiz, Fernando ;

Di Molfetta, Guglielmo ;

Meda, Francisco J. ;

Jonaitis, Erin M. ;

Koscik, Rebecca Langhough ;

Cody, Karly ;

Betthauser, Tobey J. ;

Li, Yan ;

Vanmechelen, Eugeen ;

Palmqvist, Sebastian ;

Stomrud, Erik ;

Bateman, Randall J. ;

Zetterberg, Henrik ;

Johnson, Sterling C. ;

Blennow, Kaj ;

Hansson, Oskar .

NATURE MEDICINE, 2022, 28 (12) :2555-+

[3] Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays [J].

Ashton, Nicholas J. ;

Puig-Pijoan, Albert ;

Mila-Aloma, Marta ;

Fernandez-Lebrero, Aida ;

Garcia-Escobar, Greta ;

Gonzalez-Ortiz, Fernando ;

Kac, Przemyslaw R. ;

Brum, Wagner S. ;

Benedet, Andrea L. ;

Lantero-Rodriguez, Juan ;

Day, Theresa A. ;

Vanbrabant, Jeroen ;

Stoops, Erik ;

Vanmechelen, Eugeen ;

Triana-Baltzer, Gallen ;

Moughadam, Setareh ;

Kolb, Hartmuth ;

Ortiz-Romero, Paula ;

Karikari, Thomas K. ;

Minguillon, Carolina ;

Sanchez, Juan Jose Hernandez ;

Navalpotro-Gomez, Irene ;

Grau-Rivera, Oriol ;

Manero, Rosa Maria ;

Puente-Periz, Victor ;

de la Torre, Rafael ;

Roquer, Jaume ;

Dage, Jeff L. ;

Zetterberg, Henrik ;

Blennow, Kaj ;

Suarez-Calvet, Marc .

ALZHEIMERS & DEMENTIA, 2023, 19 (05) :1913-1924

[4] Plasma p-tau231: a new biomarker for incipient Alzheimer's disease pathology [J].

Ashton, Nicholas J. ;

Pascoal, Tharick A. ;

Karikari, Thomas K. ;

Benedet, Andrea L. ;

Lantero-Rodriguez, Juan ;

Brinkmalm, Gunnar ;

Snellman, Anniina ;

Scholl, Michael ;

Troakes, Claire ;

Hye, Abdul ;

Gauthier, Serge ;

Vanmechelen, Eugeen ;

Zetterberg, Henrik ;

Rosa-Neto, Pedro ;

Blennow, Kaj .

ACTA NEUROPATHOLOGICA, 2021, 141 (05) :709-724

[5] A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease [J].

Barthelemy, Nicolas R. ;

Li, Yan ;

Joseph-Mathurin, Nelly ;

Gordon, Brian A. ;

Hassenstab, Jason ;

Benzinger, Tammie. L. S. ;

Buckles, Virginia ;

Fagan, Anne M. ;

Perrin, Richard J. ;

Goate, Alison M. ;

Morris, John C. ;

Karch, Celeste M. ;

Xiong, Chengjie ;

Allegri, Ricardo ;

Mendez, Patricio Chrem ;

Berman, Sarah B. ;

Ikeuchi, Takeshi ;

Mori, Hiroshi ;

Shimada, Hiroyuki ;

Shoji, Mikio ;

Suzuki, Kazushi ;

Noble, James ;

Farlow, Martin ;

Chhatwal, Jasmeer ;

Graff-Radford, Neill R. ;

Salloway, Stephen ;

Schofield, Peter R. ;

Masters, Colin L. ;

Martins, Ralph N. ;

O'Connor, Antoinette ;

Fox, Nick C. ;

Levin, Johannes ;

Jucker, Mathias ;

Gabelle, Audrey ;

Lehmann, Sylvain ;

Sato, Chihiro ;

Bateman, Randall J. ;

McDade, Eric ;

Allegri, Ricardo ;

Bateman, Randy ;

Bechara, Jacob ;

Benzinger, Tammie ;

Berman, Sarah ;

Bodge, Courtney ;

Brandon, Susan ;

Brooks, William ;

Buck, Jill ;

Buckles, Virginia ;

Chea, Sochenda .

NATURE MEDICINE, 2020, 26 (03) :398-+

[6] The Sun Health Research Institute Brain Donation Program: Description and experience, 1987-2007 [J].

Beach, Thomas G. ;

Sue, Lucia I. ;

Walker, Douglas G. ;

Roher, Alex E. ;

Lue, LihFen ;

Vedders, Linda ;

Connor, Donald J. ;

Sabbagh, Marwan N. ;

Rogers, Joseph .

CELL AND TISSUE BANKING, 2008, 9 (03) :229-245

[7] Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program [J].

Beach, Thomas G. ;

Adler, Charles H. ;

Sue, Lucia I. ;

Serrano, Geidy ;

Shill, Holly A. ;

Walker, Douglas G. ;

Lue, LihFen ;

Roher, Alex E. ;

Dugger, Brittany N. ;

Maarouf, Chera ;

Birdsill, Alex C. ;

Intorcia, Anthony ;

Saxon-Labelle, Megan ;

Pullen, Joel ;

Scroggins, Alexander ;

Filon, Jessica ;

Scott, Sarah ;

Hoffman, Brittany ;

Garcia, Angelica ;

Caviness, John N. ;

Hentz, Joseph G. ;

Driver-Dunckley, Erika ;

Jacobson, Sandra A. ;

Davis, Kathryn J. ;

Belden, Christine M. ;

Long, Kathy E. ;

Malek-Ahmadi, Michael ;

Powell, Jessica J. ;

Gale, Lisa D. ;

Nicholson, Lisa R. ;

Caselli, Richard J. ;

Woodruff, Bryan K. ;

Rapscak, Steven Z. ;

Ahern, Geoffrey L. ;

Shi, Jiong ;

Burke, Anna D. ;

Reiman, Eric M. ;

Sabbagh, Marwan N. .

NEUROPATHOLOGY, 2015, 35 (04) :354-389

[8]

Beach TG, 2009, ACTA NEUROPATHOL, V117, P169, DOI 10.1007/s00401-008-0450-7

[9] Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum [J].

Benedet, Andrea L. ;

Mila-Aloma, Marta ;

Vrillon, Agathe ;

Ashton, Nicholas J. ;

Pascoal, Tharick A. ;

Lussier, Firoza ;

Karikari, Thomas K. ;

Hourregue, Claire ;

Cognat, Emmanuel ;

Dumurgier, Julien ;

Stevenson, Jenna ;

Rahmouni, Nesrine ;

Pallen, Vanessa ;

Poltronetti, Nina M. ;

Salvado, Gemma ;

Shekari, Mahnaz ;

Operto, Gregory ;

Gispert, Juan Domingo ;

Minguillon, Carolina ;

Fauria, Karine ;

Kollmorgen, Gwendlyn ;

Suridjan, Ivonne ;

Zimmer, Eduardo R. ;

Zetterberg, Henrik ;

Molinuevo, Jose Luis ;

Paquet, Claire ;

Rosa-Neto, Pedro ;

Blennow, Kaj ;

Suarez-Calvet, Marc .

JAMA NEUROLOGY, 2021, 78 (12) :1471-1483

[10] NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].

BRAAK, H ;

BRAAK, E .

ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259

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