CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

NEUROBIOLOGY OF AGING

卷:89

Article

Marizzoni, Moira¹  Ferrari, Clarissa²  Babiloni, Claudio^3,4  Albani, Diego⁵  Barkhof, Frederik^6,7,8  Cavaliere, Libera¹  Didic, Mira^9,10  Forloni, Gianluigi⁵  Fusco, Federica⁵  Galluzzi, Samantha¹  Hensch, Tilman¹¹  Jovicich, Jorge¹²  Marra, Camillo¹³  Luis Molinuevo, Jose^14,15  Nobili, Flavio^16,17  Parnetti, Lucilla¹⁸  Payoux, Pierre¹⁹  Ranjeva, Jean-Philippe^10,20  Ribaldi, Federica^1,21  Rolandi, Elena¹  Rossini, Paolo Maria²²  Salvatore, Marco²³  Soricelli, Andrea²³  Tsolaki, Magdalini²⁴  Visser, Pieter Jelle²⁵  Wiltfang, Jens^26,27,28  Richardson, Jill C.²⁹  Bordet, Regis^30,31  Blin, Olivier³²  Frisoni, Giovanni B.^33,34,35 

[1] IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Lab Neuroimaging & Alzheimers Epidemiol, Via Pilastroni 4, I-25125 Brescia, Italy

[2] IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Unit Stat, Brescia, Italy

[3] Sapienza Univ Rome, Dept Physiol & Pharmacol V Erspamer, Rome, Italy

[4] Hosp San Raffaele Cassino FR, Cassino, Italy

[5] IRCCS Ist Ric Farmacol Mario Negri, Neurosci Dept, Milan, Italy

[6] Amsterdam UMC, Dept Radiol & Nucl Med, Locat VUmc, Amsterdam, Netherlands

[7] UCL, Inst Neurol, London, England

[8] UCL, Inst Healthcare Engn, London, England

[9] Aix Marseille Univ, INS, INSERM, Marseille, France

[10] Hop Timone Adultes, AP HM, Serv Neurol & Neuropsychol, Marseille, France

[11] Univ Leipzig, Dept Psychiat & Psychotherapy, Leipzig, Germany

[12] Univ Trento, Ctr Mind Brain Sci, Trento, Italy

[13] Catholic Univ, Dept Gerontol Neurosci & Orthoped, Rome, Italy

[14] Hosp Clin Barcelona, IDIBAPS, Alzheimers Dis Unit, Barcelona, Catalunya, Spain

[15] Hosp Clin Barcelona, IDIBAPS, Other Cognit Disorders Unit, Barcelona, Catalunya, Spain

[16] Univ Genoa, Dept Neurosci DINOGMI, Genoa, Italy

[17] IRCCS Osped Policlin San Martino, Clin Neurol, Genoa, Italy

[18] Univ Perugia, Osped Santa Maria Misericordia, Clin Neurol, Perugia, Italy

[19] Univ Toulouse, Toulouse NeuroImaging Ctr, UPS, INSERM,ToNIC, Toulouse, France

[20] Aix Marseille Univ, INSERM, Marseille, France

[21] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy

[22] IRCCS San Raffaele, Area Neurosci, Rome, Italy

[23] SDN Ist Ric Diagnost & Nucleare, Naples, Italy

[24] Aristotle Univ Thessaloniki, Univ Dept Neurol 1, Thessaloniki, Makedonia, Greece

[25] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Dept Neurol, Amsterdam, Netherlands

[26] Univ Duisburg Essen, LVR Hosp Essen, Fac Med, Dept Psychiat & Psychotherapy, Essen, Germany

[27] Georg August Univ, UMG, Dept Psychiat & Psychotherapy, Gottingen, Germany

[28] Univ Aveiro, Med Sci Dept, iBiMED, Aveiro, Portugal

[29] GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England

[30] Univ Lille, CHU, INSERM, Lille, France

[31] U1171 Degenerat & Vasc Cognit Disorders, Lille, France

[32] Aix Marseille Univ, AP HM, Serv Pharmacol Clin, UMR INSERM 1106, Marseille, France

[33] Univ Hosp, Memory Clin, Geneva, Switzerland

[34] Univ Hosp, LANVIE Lab Neuroimaging Aging, Geneva, Switzerland

[35] Univ Geneva, Geneva, Switzerland

关键词: Alzheimer's disease;    Apolipoprotein E;    Mild cognitive impairment;    CSF cutoff;    Disease progression;   

DOI  :  10.1016/j.neurobiolaging.2019.12.019

来源: Elsevier

【 摘 要 】

Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEe4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOE epsilon 4 status, and sex on CSF A beta 42/P-tau distribution and cutoff extraction by applying mixture models with covariates. The A beta 42/P-tau distribution revealed the presence of 3 subgroups (AD-like, intermediate, control-like) and 2 cutoffs. The identification of the intermediate subgroup and of the higher cutoff was APOE epsilon 4 dependent in both cohorts. APOE-specific classification (higher cutoff for APOEe4thorn, lower cutoff for APOE epsilon 4-) showed higher diagnostic accuracy in identifying MCI due to AD compared to single A beta 42 and A beta 42/P-tau cutoffs. APOEe4 influences amyloid and tau CSF markers and AD progression in MCI patients supporting i) the use of APOE-specific cutoffs to identify MCI due to AD and ii) the utility of considering APOE genotype for early AD diagnosis. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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