Neuroinflammation in Alzheimer's disease

被引：4964

作者：

Heneka, Michael T. ^{[1
,2
]}

Carson, Monica J. ^{[3
]}

El Khoury, Joseph ^{[4
]}

Landreth, Gary E. ^{[5
]}

Brosseron, Frederic ^{[2
]}

Feinstein, Douglas L. ^{[6
]}

Jacobs, Andreas H. ^{[7
,8
]}

Wyss-Coray, Tony ^{[9
,10
]}

Vitorica, Javier ^{[11
]}

Ransohoff, Richard M. ^{[12
]}

Herrup, Karl ^{[13
]}

Frautschy, Sally A. ^{[14
]}

Finsen, Bente ^{[15
]}

Brown, Guy C. ^{[16
]}

Verkhratsky, Alexei ^{[17
,18
,19
]}

Yamanaka, Koji ^{[20
]}

Koistinaho, Jari ^{[21
]}

Latz, Eicke ^{[2
,22
,23
]}

Halle, Annett ^{[24
]}

Petzold, Gabor C. ^{[1
,2
]}

Town, Terrence ^{[25
]}

Morgan, Dave ^{[26
]}

Shinohara, Mari L. ^{[27
]}

Perry, V. Hugh ^{[28
]}

Holmes, Clive ^{[29
,30
]}

Bazan, Nicolas G. ^{[31
]}

Brooks, David J. ^{[32
]}

Hunot, Stephane ^{[33
]}

Joseph, Bertrand ^{[34
]}

Deigendesch, Nikolaus ^{[35
]}

Garaschuk, Olga ^{[36
]}

Boddeke, Erik ^{[37
]}

Dinarello, Charles A. ^{[38
]}

Breitner, John C. ^{[39
,40
]}

Cole, Greg M. ^{[14
]}

Golenbock, Douglas T. ^{[23
]}

Kummer, Markus P.

机构：

[1] Univ Bonn, Dept Neurol, Univ Hosp Bonn, D-53127 Bonn, Germany

[2] German Ctr Neurodegnerat Dis DZNE, Bonn, Germany

[3] Univ Calif Riverside, Div Biomed Sci, Ctr Glial Neuronal Interact, Riverside, CA 92521 USA

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA USA

[5] Case Western Reserve Univ, Sch Med, Dept Neurosci, Alzheimer Res Lab, Cleveland, OH 44106 USA

[6] Univ Illinois, Dept Anesthesiol, Chicago, IL USA

[7] Johanniter Hosp, Dept Geriatr, Bonn, Germany

[8] Westfalian Wilhelms Univ WWU, European Inst Mol Imaging EIMI, Munster, Germany

[9] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[10] VA Palo Alto Hlth Care Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA USA

[11] Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, Consejo Super Invest Cient, Seville, Spain

[12] Cleveland Clin, Lerner Res Inst, Neuroinflammat Res Ctr, Dept Neurosci, Cleveland, OH 44106 USA

[13] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China

[14] Univ Calif Los Angeles, David Geffen Sch Med, Geriatr Res & Clin Ctr, Dept Neurol,Greater Los Angeles Vet Affairs Healt, Los Angeles, CA 90095 USA

[15] Univ Southern Denmark, Inst Mol Med, Odense, Denmark

[16] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

[17] Univ Manchester, Fac Life Sci, Manchester, Lancs, England

[18] Basque Fdn Sci IKERBASQUE, Achucarro Ctr Neurosci, Bilbao, Spain

[19] Univ Basque Country, Univ Basque Country UPV, Dept Neurosci,EHU Euskal Herriko Unibertsitatea, CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Leioa, Spain

[20] Nagoya Univ, RIKEN Brain Sci Inst, Environm Med Res Inst, Wako, Saitama, Japan

[21] Univ Eastern Finland, Al Virtanen Inst Mol Sci, Dept Neurobiol, Kuopio, Finland

[22] Univ Bonn, Inst Innate Immun, D-53127 Bonn, Germany

[23] Univ Massachusetts, Sch Med, Dept Infect Dis & Immunol, Worcester, MA USA

[24] Ctr Adv European Studies & Res CAESAR, Max Planck Res Grp Neuroimmunol, Bonn, Germany

[25] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA

[26] Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, Byrd Alzheimers Inst, Tampa, FL USA

[27] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA

[28] Southampton Gen Hosp, Sch Biol Sci, Southampton SO9 4XY, Hants, England

[29] Univ Southampton, Clin & Expt Sci, Southampton, Hants, England

[30] Southern Hlth Fdn Trust, Moorgreen Hosp, Memory Assessment & Res Ctr, Southampton, Hants, England

[31] Louisiana State Univ, Neurosci Ctr Excellence, Sch Med, New Orleans, LA USA

[32] Univ London Imperial Coll Sci Technol & Med, Div Expt Med, Hammersmith Hosp, London, England

[33] CNRS, UMR 7225, Expt Therapeut Neurodegenerat, Paris, France

[34] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden

[35] Max Planck Inst Infect Biol, Dept Cellular Microbiol, Berlin, Germany

[36] Univ Tubingen, Inst Physiol 2, Tubingen, Germany

[37] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Groningen, Netherlands

[38] Univ Colorado Denver, Dept Med, Aurora, CO USA

[39] Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada

[40] McGill Univ, Fac Med, Montreal, PQ, Canada

来源：

LANCET NEUROLOGY | 2015年 / 14卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; TRAUMATIC BRAIN-INJURY; TRANSGENIC MOUSE MODEL; ANTIINFLAMMATORY PREVENTION TRIAL; NITRIC-OXIDE SYNTHASE; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL AMYLOID ANGIOPATHY; GENOME-WIDE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM;

D O I：

10.1016/S1474-4422(15)70016-5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

引用

页码：388 / 405

页数：18

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