Inflammatory biomarkers in Alzheimer's disease plasma

Por: Leckey, C, Nevado-Holgado, AJ, Barkhof, F, Bertram, L, Blin, O, Bos, I, Dobricic, V, Engelborghs, S, Frisoni, G, Frolich, L, Gabel, S, Johannsen, P, Kettunen, P, Koszewska, I, Legido-Quigley, C, Lleo, A, Martinez-Lage, P, Mecocci, P, Meersmans, K, Molinuevo, JL, Peyratout, G, Popp, J, Richardson, J, Sala, I, Scheltens, P, Streffer, J, Soininen, H, Tainta-Cuezva, M, Teunissen, C, Tsolaki, M, Vandenberghe, R, Visser, PJ, Vos, S, Wahlund, LO, Wallin, A, Westwood, S, Zetterberg, H, Bullmore, ET, Bhatti, J, Chamberlain, SJ, Correia, MM, Crofts, AL, Dickinson, A, Foster, AC, Kitzbichler, MG, Knight, C, Lynall, ME, Maurice, C, O'Donnell, C, Pointon, LJ, Hyslop, PS, Turner, L, Vertes, P, Widmer, B, Williams, GB, Morgan, BP, Leckey, C, Morgan, AR, O'Hagan, C, Touchard, S, Cavanagh, J, Deith, C, Farmer, S, McClean, J, McColl, A, McPherson, A, Scouller, P, Sutherland, M, Boddeke, HWGM, Richardson, JC, Khan, S, Murphy, P, Parker, CA, Patel, J, Jones, D, Boer, P, Kemp, J, Drevets, WC, Nye, JS, Wittenberg, G, Isaac, J, Bhattacharya, A, Carruthers, N, Kolb, H, Pariante, CM, Turkheimer, F, Barker, GJ, Byrom, H, Cash, D, Cattaneo, A, Gee, A, Hastings, C, Mariani, N, McLaughlin, A, Mondelli, V, Nettis, M, Nikkheslat, N, Randall, K, Sheridan, H, Simmons, C, Singh, N, Van Loo, V, Vicente-Rodriguez, M, Wood, TC, Worrell, C, Zajkowska, Z, Plath, N, Egebjerg, J, Eriksson, H, Gastambide, F, Adams, KH, Jeggo, R, Thomsen, C, Pederson, JT, Campbell, B, Moller, T, Nelson, B, Zorn, S, O'Connor, J, Attenburrow, MJ, Baird, A, Benjamin, J, Clare, S, Cowen, P, Huang, IS, Hurley, S, Jones, H, Lovestone, S, Mada, F, Nevado-Holgado, A, Oladejo, A, Ribe, E, Smith, K, Vyas, A, Hughes, Z, Balice-Gordon, R, Duerr, J, Piro, JR, Sporn, J, Perry, VH, Cleal, M, Fryatt, G, Gomez-Nicola, D, Mancuso, R, Reynolds, R, Harrison, NA, Cercignani, M, Clarke, CL, Hoskins, E, Kohn, C, Murray, R, Wilcock, L, Wlazly, D, NIMA Consortium, NIMA-Wellcome Trust Consortium

Publicada: 1 jun 2019

Web: https://europepmc.org/article/MED/31047856

Resumen:
Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOe4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Filiaciones:
Leckey, C:
Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Sch Med, UK Dementia Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Cardiff CF10 3AT, S Glam, Wales

Nevado-Holgado, AJ:
Univ Oxford, Dept Psychiat, Oxford, England

Barkhof, F:
VU Univ Med, Dept Radiol & Nucl Med, Amsterdam, Netherlands

UCL, UCL Inst Neurol & Healthcare Engn, London, England

Bertram, L:
Max Planck Inst Mol Genet, Berlin, Germany

Blin, O:
Aix Marseille Univ, APHM, Inst Neurosci Syst, Pharmacol, Marseille, France

Bos, I:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands

Dobricic, V:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany

Engelborghs, S:
Hosp Network Antwerp ZNA, Dept Neurol, Antwerp, Belgium

Inst Born Bunge, Ref Ctr Biol Markers Dementia, Antwerp, Belgium

Frisoni, G:
Univ Geneva, Geneva, Switzerland

IRCCS Ist Ctr San Giovanni Dio Fatebenefratell, Brescia, Italy

Frolich, L:
Heidelberg Univ, Zentralinst Seel Gesundheit, Dept Geriatr Psychiat, Mannheim, Germany

Gabel, S:
Katholieke Univ Leuven, Lab Cognit Neurol, Dept Neurosci, Leuven, Belgium

Johannsen, P:
Karolinska Inst, Dept Neurobiol Caring Sci & Soc, Div Clin Geriatr, Stockholm, Sweden

Kettunen, P:
Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden

Koszewska, I:
Med Univ Lodz, Dept Old Age Psychiat & Psychot Disorders, Lodz, Poland

Legido-Quigley, C:
UCL, UCL Inst Neurol & Healthcare Engn, London, England

Imperial Coll London, Sch Publ Hlth, London, England

Lleo, A:
Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona, Spain

Martinez-Lage, P:
CITA Alzheimer Fdn, San Sebastian, Spain

Mecocci, P:
Univ Perugia, Inst Gerontol & Geriatr, Dept Med, Perugia, Italy

Molinuevo, JL:
Unversitat Pompeu Fabra, Barcelona Beta Brain Res Ctr, Barcelona, Spain

Peyratout, G:
Lausanne Univ Hosp, Old Age Psychiat, Dept Psychiat, Lausanne, Switzerland

Popp, J:
Univ Geneva, Geneva, Switzerland

Hopitaux Univ Geneve, Geneva, Switzerland

Richardson, J:
GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England

GlaxoSmithKline R&D, Neurosci Virtual PoC DPU, Stevenage SG1 2NY, Herts, England

Sala, I:
Hosp Santa Creu & Sant Pau, Neurol Dept, Memory Unit, Barcelona, Spain

Scheltens, P:
Vrije Univ, Amsterdam Univ Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands

Streffer, J:
Univ Antwerp, Inst Born Bunge, Ref Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium

Soininen, H:
Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland

Tainta-Cuezva, M:
CITA Alzheimer Fdn, Ctr Res & Adv Therapies, San Sebastian, Spain

Teunissen, C:
Univ Hosp Leuven, Leuven, Belgium

Tsolaki, M:
AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki, Greece

Vandenberghe, R:
Univ Amsterdam, Med Ctr, Neurochem lab, Dept Clin Chem, Amsterdam, Netherlands

Visser, PJ:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands

Wahlund, LO:
Karolinska Inst, Sect Clin Geriatr, NVS Dept, Huddinge, Sweden

Wallin, A:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sect Psychiat & Neurochem, Gothenburg, Sweden

Westwood, S:
Univ Oxford, Dept Psychiat, Oxford, England

Zetterberg, H:
Sahlgrens Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden

Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Molndal, Sweden

UCL Inst Neurol, Dept Mol Neurosci, London, England

UK Dementia Res Inst, London, England

Bullmore, ET:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge CB21 5EF, England

GlaxoSmithKline R&D, Immunopsychiat, Immunoinflammat Therapeut Area Unit, Stevenage SG1 2NY, Herts, England

Bhatti, J:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Chamberlain, SJ:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge CB21 5EF, England

Correia, MM:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

MRC Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England

Crofts, AL:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Kitzbichler, MG:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Lynall, ME:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Maurice, C:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

O'Donnell, C:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Pointon, LJ:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Hyslop, PS:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Tanz Ctr Res Neurodegenerat Dis, 60 Leonard Ave, Toronto, ON M5T 2S8, Canada

Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0SZ, England

Turner, L:
Univ Cambridge, Sch Clin Med, Dept Med, Cambridge CB2 0SZ, England

Vertes, P:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Widmer, B:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Williams, GB:
Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge CB2 0SZ, England

Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0SZ, England

Morgan, BP:
Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Sch Med, UK Dementia Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Cardiff CF10 3AT, S Glam, Wales

Leckey, C:
Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Sch Med, UK Dementia Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Cardiff CF10 3AT, S Glam, Wales

Morgan, AR:
Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Sch Med, UK Dementia Res Inst, Cardiff, S Glam, Wales

O'Hagan, C:
Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Sch Med, UK Dementia Res Inst, Cardiff, S Glam, Wales

Touchard, S:
Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Sch Med, UK Dementia Res Inst, Cardiff, S Glam, Wales

Cardiff Univ, Cardiff CF10 3AT, S Glam, Wales

Cavanagh, J:
Univ Glasgow, Inst Hlth & Wellbeing, Sackler Ctr, Sir Graeme Davies Bldg, Glasgow G12 8TA, Lanark, Scotland

Farmer, S:
NHS Greater Glasgow & Clyde, 1055 Great Western Rd, Glasgow G12 0XH, Lanark, Scotland

McClean, J:
NHS Greater Glasgow & Clyde, 1055 Great Western Rd, Glasgow G12 0XH, Lanark, Scotland

McColl, A:
Univ Glasgow, Inst Hlth & Wellbeing, Sackler Ctr, Sir Graeme Davies Bldg, Glasgow G12 8TA, Lanark, Scotland

Sutherland, M:
NHS Greater Glasgow & Clyde, 1055 Great Western Rd, Glasgow G12 0XH, Lanark, Scotland

Boddeke, HWGM:
Univ Groningen, NL-9712 CP Groningen, Netherlands

Richardson, JC:
GlaxoSmithKline R&D, Neurosci Virtual PoC DPU, Stevenage SG1 2NY, Herts, England

Khan, S:
GlaxoSmithKline R&D, Immunopsychiat, Immunoinflammat Therapeut Area Unit, Stevenage SG1 2NY, Herts, England

Murphy, P:
GlaxoSmithKline R&D, Expt Med Imaging, Stevenage SG1 2NY, Herts, England

Parker, CA:
GlaxoSmithKline R&D, Expt Med Imaging, Stevenage SG1 2NY, Herts, England

Patel, J:
GlaxoSmithKline R&D, Immunopsychiat, Immunoinflammat Therapeut Area Unit, Stevenage SG1 2NY, Herts, England

Boer, P:
Janssen Pharmaceut NV, Neurosci, Janssen Res & Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium

Kemp, J:
Janssen Pharmaceut NV, Neurosci, Janssen Res & Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium

Drevets, WC:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Nye, JS:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Wittenberg, G:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Isaac, J:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Bhattacharya, A:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Carruthers, N:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Kolb, H:
Janssen Res & Dev LLC, Neurosci, Titusville, NJ 08560 USA

Pariante, CM:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Turkheimer, F:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Barker, GJ:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Byrom, H:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Cash, D:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Cattaneo, A:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Gee, A:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Hastings, C:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Mariani, N:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

McLaughlin, A:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Mondelli, V:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Nettis, M:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Nikkheslat, N:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London SE5 9RT, England

Randall, K:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Simmons, C:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Singh, N:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Vicente-Rodriguez, M:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Wood, TC:
Kings Coll London, Dept Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Crespigny Pk, London SE5 8AF, England

Plath, N:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Egebjerg, J:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Eriksson, H:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Gastambide, F:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Adams, KH:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Jeggo, R:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Thomsen, C:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

Pederson, JT:
H Lundbeck & Co AS, Ottiliavej 9, DK-2500 Valby, Denmark

O'Connor, J:
Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA

Attenburrow, MJ:
Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

Warneford Hosp, NIHR Oxford Cognit Hlth Clin Res Facil, Oxford OX3 7JX, England

Baird, A:
Warneford Hosp, NIHR Oxford Cognit Hlth Clin Res Facil, Oxford OX3 7JX, England

Benjamin, J:
Warneford Hosp, NIHR Oxford Cognit Hlth Clin Res Facil, Oxford OX3 7JX, England

Clare, S:
John Radcliffe Hosp, Oxford Ctr Funct MRI Brain, Oxford OX3 9DU, England

Cowen, P:
Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

Huang, IS:
Kennedy Inst Rheumatol, Oxford OX3 7FY, England

Jones, H:
Warneford Hosp, NIHR Oxford Cognit Hlth Clin Res Facil, Oxford OX3 7JX, England

Lovestone, S:
Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

Nevado-Holgado, A:
Univ Oxford, Dept Psychiat, Oxford, England

Ribe, E:
Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

Smith, K:
Warneford Hosp, NIHR Oxford Cognit Hlth Clin Res Facil, Oxford OX3 7JX, England

Perry, VH:
Univ Southampton, Ctr Biol Sci, Southampton, Hants, England

Fryatt, G:
Univ Southampton, Ctr Biol Sci, Southampton, Hants, England

Gomez-Nicola, D:
Univ Southampton, Ctr Biol Sci, Southampton, Hants, England

Mancuso, R:
VIB KU Leuven, Ctr Brain & Dis Res Campus Gasthuisberg, Herestraat 49,Bus 602, B-3000 Leuven, Belgium

Reynolds, R:
Univ Southampton, Ctr Biol Sci, Southampton, Hants, England

Harrison, NA:
Univ Sussex, CISC, Brighton BN1 9RR, E Sussex, England

Cercignani, M:
Univ Sussex, CISC, Brighton BN1 9RR, E Sussex, England

Clarke, CL:
Univ Sussex, CISC, Brighton BN1 9RR, E Sussex, England

Wilcock, L:
Sussex Partnership NHS Fdn Trust, Nevill Ave, Hove BN3 7HZ, England

Wlazly, D:
Brighton & Sussex Univ Hosp NHS Trust, Brighton BN2 5BE, E Sussex, England

Maurice Wohl Clin Neurosci Inst, Cutcombe Rd, London SE5 9RT, England.
Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9RR, E Sussex, England.
Sussex Partnership NHS Fdn Trust, Swandean BN13 3EP, England.
Pfizer Inc, 1 Portland St, Cambridge, MA USA.

ISSN: 15525260

Alzheimers & Dementia

Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America

Tipo de documento: Article
Volumen: 15 Número: 6
Páginas: 776-787

DOI: 10.1016/j.jalz.2019.03.007

WOS Id: 000470084500005

ID de PubMed: 31047856

Inflammatory biomarkers in Alzheimer's disease plasma

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