Plasma Aβ42 as a Biomarker of Prodromal Alzheimer's Disease Progression in Patients with Amnestic Mild Cognitive Impairment: Evidence from the PharmaCog/E-ADNI Study

被引：20

作者：

Albani, Diego ^{[1
]}

Marizzoni, Moira ^{[2
]}

Ferrari, Clarissa ^{[3
]}

Fusco, Federica ^{[1
]}

Boeri, Lucia ^{[1
]}

Raimondi, Ilaria

Jovicich, Jorge ^{[4
]}

Babiloni, Claudio ^{[5
,6
]}

Soricelli, Andrea ^{[7
]}

Lizio, Roberta ^{[5
]}

Galluzzi, Samantha ^{[2
]}

Cavaliere, Libera ^{[2
]}

Didic, Mira ^{[8
,9
]}

Schoenknecht, Peter ^{[10
]}

Luis Molinuevo, Jose ^{[11
,12
]}

Nobili, Flavio ^{[13
,14
]}

Parnetti, Lucilla ^{[15
]}

Payoux, Pierre ^{[16
]}

Bocchio, Luisella ^{[17
,18
]}

Salvatore, Marco ^{[7
]}

Rossini, Paolo Maria ^{[19
,20
]}

Tsolaki, Magda ^{[21
]}

Visser, Pieter Jelle ^{[22
]}

Richardson, Jill C. ^{[23
]}

Wiltfang, Jens ^{[24
,25
,26
]}

Bordet, Regis ^{[27
]}

Blin, Olivier ^{[28
]}

Forloni, Gianluigi ^{[1
]}

Frisoni, Giovanni B. ^{[29
,30
]}

机构：

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

[2] IRCCS, Ist Ctr San Giovanni di Dio, Lab Neuroimaging & Alzheimers, Brescia, Italy

[3] IRCCS Ist Centro San Giovanni Dio Fatebenefratell, Unit Stat, Brescia, Italy

[4] Univ Trento, DMR Lab Head, Ctr Mind Brain Sci, Trento, Italy

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

[6] IRCCS San Raffaele Pisana Rome & Cassino, Dept Neurosci, Rome, Italy

[7] IRCCS SDN Ist Ric Diagnost Nucl, Naples, Italy

[8] Aix Marseille Univ, INSERM, INS UMR S 1106, Marseille, France

[9] APHM Hop Timone Adultes, APHM, Timone Serv Neurol & Neuropsychol, Marseille, France

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

[11] Hosp Clin Barcelona, Alzheimers Dis Unit & Other Cognit Disorders Unit, Barcelona, Catalunya, Spain

[12] Inst Invest Biomed August Pi Sunyer IDIBAPS, Barcelona, Catalunya, Spain

[13] Univ Genoa, Clin Neurol, Dept Neuroscience ( DINOGMI), Genoa, Italy

[14] IRCCS AOU San Martino IST, Genoa, Italy

[15] Univ Perugia, Clin Neurol, Osped St Maria Misericordia, Perugia, Italy

[16] INSERM, Imagerie Cerebrate & Handicaps Neurol, UMR 825, Toulouse, France

[17] IRCCS Ctr Giovanni Dio, Genet Unit, Fatebenefratelli, Brescia, Italy

[18] Univ eCampus, Novedrate, Como, Italy

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

[20] Policlin A Gemelli Fdn, Rome, Italy

[21] Aristotle Univ Thessaloniki, G Papanikolaou Hosp, Sch Med, Neurol Clin 3, Thessaloniki, Greece

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

[23] GlaxoSmithKline R&D, Neurosci Therapeut Area, Gunnels Wood Rd, Stevenage, Herts, England

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

[25] Georg August Univ, Univ Med Ctr ( UMG), Dept Psychiat & Psychotherapy, Gottingen, Germany

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

[27] Univ Lille, INSERM, CHU Lille, U1171 Degenerat & Vasc Cognit Disorders, Lille, France

[28] Aix Marseille Univ, Serv Pharmacol Clin, AP HM, UMR CNRS 7289, Marseille, France

[29] Univ Hosp, Memory Clin & LANVIE Lab Neuroimaging Aging, Geneva, Switzerland

[30] Univ Geneva, Geneva, Switzerland

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2019年 / 69卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

Amnesic mild cognitive impairment; amyloid-beta peptide; biomarkers; clinical trial; clusterin; PharmaCog project; prodromal Alzheimer's disease; CLUSTERIN; ASSOCIATION; RISK; CR-1; CLU; CSF;

D O I：

10.3233/JAD-180321

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

It is an open issue whether blood biomarkers serve to diagnose Alzheimer's disease (AD) or monitor its progression over time from prodromal stages. Here, we addressed this question starting from data of the European FP7 IMI-PharmaCog/E-ADNI longitudinal study in amnesic mild cognitive impairment (aMCI) patients including biological, clinical, neuropsychological (e.g., ADAS-Cog13), neuroimaging, and electroencephalographic measures. PharmaCog/E-ADNI patients were classified as "positive" (i.e., "prodromal AD"; n = 76) or "negative" (n = 52) based on a diagnostic cut-off of A beta(42)/P-tau in cerebrospinal fluid as well as APOE epsilon 4 genotype. Blood was sampled at baseline and at two followups (12 and 18 months), when plasma amyloid peptide 42 and 40 (A beta(42), A beta(40)) and apolipoprotein J (clusterin, CLU) were assessed. Linear Mixed Models found no significant differences in plasma molecules between the "positive" (i. e., prodromal AD) and "negative" groups at baseline. In contrast, plasma A beta(42) showed a greater reduction over time in the prodromal AD than the "negative" aMCI group (p = 0.048), while CLU and A beta(40) increased, but similarly in the two groups. Furthermore, plasma A beta(42) correlated with the ADAS-Cog13 score both in aMCI patients as a whole and the prodromal AD group alone. Finally, CLU correlated with the ADAS-Cog13 only in the whole aMCI group, and no association with ADAS-Cog13 was found for A beta(40). In conclusion, plasma A beta(42) showed disease progression-related features in aMCI patients with prodromal AD.

引用

页码：37 / 48

页数：12

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