Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology

被引：5

作者：

Bloemeke, Lara ^{[1
,2
,3
]}

Rehn, Fabian ^{[1
,2
,3
]}

Kraemer-Schulien, Victoria ^{[1
]}

Kutzsche, Janine ^{[1
]}

Pils, Marlene ^{[1
,2
,3
]}

Bujnicki, Tuyen ^{[1
]}

Lewczuk, Piotr ^{[4
]}

Kornhuber, Johannes ^{[4
]}

Freiesleben, Silka D. ^{[5
,6
]}

Schneider, Luisa-Sophie ^{[5
]}

Preis, Lukas ^{[5
]}

Priller, Josef ^{[5
,6
,7
,8
]}

Spruth, Eike J. ^{[5
,6
]}

Altenstein, Slawek ^{[5
,6
]}

Lohse, Andrea ^{[5
]}

Schneider, Anja ^{[9
,10
]}

Fliessbach, Klaus ^{[9
,10
]}

Wiltfang, Jens ^{[11
,12
,13
]}

Hansen, Niels ^{[12
]}

Rostamzadeh, Ayda ^{[14
]}

Duezel, Emrah ^{[15
,16
]}

Glanz, Wenzel ^{[15
]}

Incesoy, Enise I. ^{[15
,16
,17
]}

Butryn, Michaela ^{[15
]}

Buerger, Katharina ^{[18
,19
]}

Janowitz, Daniel ^{[19
]}

Ewers, Michael ^{[18
,19
]}

Perneczky, Robert ^{[18
,20
,21
,22
]}

Rauchmann, Boris-Stephan ^{[20
,23
,24
]}

Teipel, Stefan ^{[25
,26
]}

Kilimann, Ingo ^{[25
,26
]}

Goerss, Doreen ^{[25
,26
]}

Laske, Christoph ^{[27
,28
]}

Munk, Matthias H. ^{[27
,29
]}

Sanzenbacher, Carolin ^{[27
]}

Spottke, Annika ^{[9
,30
]}

Roy-Kluth, Nina ^{[9
]}

Heneka, Michael T. ^{[31
]}

Brosseron, Frederic ^{[9
]}

Wagner, Michael ^{[9
,10
]}

Wolfsgruber, Steffen ^{[9
,10
]}

Kleineidam, Luca ^{[9
,10
]}

Stark, Melina ^{[10
]}

Schmid, Matthias ^{[9
,32
]}

Jessen, Frank ^{[9
,14
,33
]}

Bannach, Oliver ^{[1
,2
]}

Willbold, Dieter ^{[1
,2
,3
]}

Peters, Oliver ^{[5
,6
]}

机构：

[1] Forschungszentrum Julich, Inst Biol Informat Proc Struct Biochem IBI 7, Wilhelm Johnen Str, D-52428 Julich, Germany

[2] attyloid GmbH, Merowingerpl 1a, D-40225 Dusseldorf, Germany

[3] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, Dusseldorf, Germany

[4] Univ Klinikum Erlangen & Friedrich Alexander Univ, Dept Psychiat & Psychotherapy, Erlangen, Germany

[5] Charite, Dept Psychiat & Psychotherapy, Berlin, Germany

[6] German Ctr Neurodegenerat Dis DZNE, Berlin, Germany

[7] Tech Univ Munich, Sch Med, Dept Psychiat & Psychotherapy, Munich, Germany

[8] Univ Edinburgh & UK DRI, Edinburgh, Scotland

[9] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[10] Univ Bonn, Med Ctr, Dept Neurodegenerat Dis & Geriatr Psychiat Psychia, Bonn, Germany

[11] German Ctr Neurodegenerat Dis DZNE, Gottingen, Germany

[12] Univ Gottingen, Dept Psychiat & Psychotherapy, Univ Med Ctr Gottingen, Gottingen, Germany

[13] Univ Aveiro, Inst Biomed iBiMED, Dept Med Sci, Neurosci & Signaling Grp, Aveiro, Portugal

[14] Univ Cologne, Fac Med, Dept Psychiat, Cologne, Germany

[15] German Ctr Neurodegenerat Dis DZNE, Magdeburg, Germany

[16] Otto von Guericke Univ, Inst Cognit Neurol & Dementia Res IKND, Magdeburg, Germany

[17] Univ Magdeburg, Dept Psychiat & Psychotherapy, Magdeburg, Germany

[18] German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany

[19] Ludwig Maximilians Univ Munchen, Inst Stroke & Dementia Res ISD, Univ Hosp, Munich, Germany

[20] Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany

[21] Munich Cluster Syst Neurol SyNergy Munich, Munich, Germany

[22] Imperial Coll London, Sch Publ Hlth, Ageing Epidemiol Res Unit AGE, London, England

[23] Univ Sheffield, Sheffield Inst Translat Neurosci SITraN, Sheffield, England

[24] Univ Hosp LMU, Dept Neuroradiol, Munich, Germany

[25] German Ctr Neurodegenerat Dis DZNE, Rostock, Germany

[26] Rostock Univ, Med Ctr, Dept Psychosomat Med, Rostock, Germany

[27] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[28] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Psychiat & Psychotherapy, Sect Dementia Res, Tubingen, Germany

[29] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany

[30] Univ Bonn, Dept Neurol, Bonn, Germany

[31] Univ Luxembourg, Luxembourg Ctr Syst Biomed LCSB, Belvaux, Luxembourg

[32] Univ Hosp Bonn, Inst Med Biometry, Bonn, Germany

[33] Univ Cologne, Excellence Cluster Cellular Stress Responses Aging, Cologne, Germany

来源：

ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING | 2024年 / 16卷 / 02期

关键词：

Alzheimer's disease; APOE; AT(N) classification; A beta; cerebrospinal fluid; oligomers; preclinical; prodromal; sFIDA; tau; CEREBROSPINAL-FLUID; RESEARCH FRAMEWORK; COGNITIVE DECLINE; BIOMARKERS; NEURODEGENERATION; QUANTITATION; STANDARDS; DIAGNOSIS;

D O I：

10.1002/dad2.12589

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION: Soluble amyloid beta (A beta) oligomers have been suggested as initiating A beta related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS: A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. A beta and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS: Across groups, highest A beta oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. A beta oligomers were significantly higher in A+T- compared to A-T- and A+T+. APOE epsilon 4 allele carriers showed significantly higher A beta oligomer levels. No differences in tau oligomers were detected. DISCUSSION: The accumulation of A beta oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting A beta oligomers might have the highest therapeutic effect in these disease stages.

引用

页数：12

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