Alternatives to amyloid for Alzheimer's disease therapies-a symposium report

被引：7

作者：

Cable, Jennifer

Holtzman, David M. ^{[1
]}

Hyman, Bradley T. ^{[2
]}

Tansey, Malu Gamez ^{[3
]}

Colonna, Marco ^{[4
]}

Kellis, Manolis ^{[5
,6
]}

Brinton, Roberta D. ^{[7
,8
]}

Albert, Marilyn ^{[9
]}

Wellington, Cheryl L. ^{[10
]}

Sisodia, Sangram S. ^{[11
,12
]}

Tanzi, Rudolph E. ^{[13
]}

机构：

[1] Washington Univ, Dept Neurol, St Louis, MO 63110 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA

[3] Univ Florida, Coll Med, McKnight Brain Inst, Dept Neurosci,Ctr Translat Res Neurodegenerat Dis, Gainesville, FL USA

[4] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[5] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[7] Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA

[8] Univ Arizona, Coll Med, Dept Neurol, Tucson, AZ 85724 USA

[9] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[10] Univ British Columbia, Sch Biomed Engn, Collaborat Repair Discoveries, Dept Pathol & Lab Med,Djavad Mowafaghian Ctr Brai, Vancouver, BC, Canada

[11] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA

[12] Univ Chicago, Microbiome Ctr, Chicago, IL 60637 USA

[13] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA

来源：

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES | 2020年 / 1475卷 / 01期

关键词：

Alzheimer's disease; amyloid; allopregnanolone; APOE; cognitive impairment; dementia; HDL; microbiome; microglia; neuroinflammation; tau; TREM2; MILD COGNITIVE IMPAIRMENT; HIGH-DENSITY-LIPOPROTEIN; HIPPOCAMPAL ACTIVATION; MICROGLIAL RESPONSE; MOUSE MODEL; ALLOPREGNANOLONE; DEFICITS; PROLIFERATION; SURVIVAL; MEMORY;

D O I：

10.1111/nyas.14371

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

For decades, Alzheimer's disease research has focused on amyloid as the primary pathogenic agent. This focus has driven the development of numerous amyloid-targeting therapies; however, with one possible exception, none of these therapies have been effective in preventing or delaying cognitive decline in patients, and there are no approved disease-modifying agents. It is becoming more apparent that alternative drug targets are needed to address this complex disease. An increased understanding of Alzheimer's disease pathology has highlighted the need to target the appropriate disease pathology at the appropriate time in the disease course. Preclinical and early clinical studies have focused on targets, including inflammation, tau, vascular health, and the microbiome. This report summarizes the presentations from a New York Academy of Sciences' one-day symposium entitled "Alzheimer's Disease Therapeutics: Alternatives to Amyloid," held on November 20, 2019.

引用

页码：3 / 14

页数：12

共 90 条

[31] TREM2 Variants in Alzheimer's Disease [J].

Guerreiro, Rita ;

Wojtas, Aleksandra ;

Bras, Jose ;

Carrasquillo, Minerva ;

Rogaeva, Ekaterina ;

Majounie, Elisa ;

Cruchaga, Carlos ;

Sassi, Celeste ;

Kauwe, John S. K. ;

Lupton, Michelle K. ;

Ryten, Mina ;

Brown, Kristelle ;

Lowe, James ;

Ridge, Perry G. ;

Hammer, Monia B. ;

Wakutani, Yosuke ;

Proitsi, Petroula ;

Newhouse, Stephen ;

Lohmann, Ebba ;

Erginel-Unaltuna, Nihan ;

Medway, Christopher ;

Hanagasi, Hasmet ;

Troakes, Claire ;

Gurvit, Hakan ;

Bilgic, Basar ;

Al-Sarraj, Safa ;

Benitez, Bruno ;

Cooper, Breanna ;

Carrell, David ;

Emre, Murat ;

Zou, Fanggeng ;

Ma, Li ;

Murray, Melissa E. ;

Dickson, Dennis W. ;

Younkin, Steven ;

Hazrati, Lilinaz ;

Petersen, Ronald C. ;

Corcoran, Christopher D. ;

Cai, Yefei ;

Oliveira, Catarina ;

Ribeiro, Maria Helena ;

Santana, Isabel ;

Tschanz, JoAnn T. ;

Gibbs, J. Raphael ;

Norton, Maria C. ;

Kloszewska, Iwona ;

Mecocci, Patrizia ;

Soininen, Hilkka ;

Tsolaki, Magda ;

Vellas, Bruno .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (02) :117-127

[32] The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans [J].

Holth, Jerrah K. ;

Fritschi, Sarah K. ;

Wang, Chanung ;

Pedersen, Nigel P. ;

Cirrito, John R. ;

Mahan, Thomas E. ;

Finn, Mary Beth ;

Manis, Melissa ;

Geerling, Joel C. ;

Fuller, Patrick M. ;

Lucey, Brendan P. ;

Holtzman, David M. .

SCIENCE, 2019, 363 (6429) :880-883

[33] Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression [J].

Huijbers, Willem ;

Mormino, Elizabeth C. ;

Schultz, Aaron P. ;

Wigman, Sarah ;

Ward, Andrew M. ;

Larvie, Mykol ;

Amariglio, Rebecca E. ;

Marshall, Gad A. ;

Rentz, Dorene M. ;

Johnson, Keith A. ;

Sperling, Reisa A. .

BRAIN, 2015, 138 :1023-1035

[34] Synthetic Tau Fibrils Mediate Transmission of Neurofibrillary Tangles in a Transgenic Mouse Model of Alzheimer's-Like Tauopathy [J].

Iba, Michiyo ;

Guo, Jing L. ;

McBride, Jennifer D. ;

Zhang, Bin ;

Trojanowski, John Q. ;

Lee, Virginia M-Y .

JOURNAL OF NEUROSCIENCE, 2013, 33 (03) :1024-1037

[35]

International Alzheimer's and Related Dementias Research Portfolio (IADRP), 2019, A3 STUD ANT AM PREV

[36] Allopregnanolone Preclinical Acute Pharmacokinetic and Pharmacodynamic Studies to Predict Tolerability and Efficacy for Alzheimer's Disease [J].

Irwin, Ronald W. ;

Solinsky, Christine M. ;

Loya, Carlos M. ;

Salituro, Francesco G. ;

Rodgers, Kathleen E. ;

Bauer, Gerhard ;

Rogawski, Michael A. ;

Brinton, Roberta Diaz .

PLOS ONE, 2015, 10 (06)

[37] Frontiers in therapeutic development of allopregnanolone for Alzheimer's disease and other neurological disorders [J].

Irwin, Ronald W. ;

Solinsky, Christine M. ;

Brinton, Roberta Diaz .

FRONTIERS IN CELLULAR NEUROSCIENCE, 2014, 8

[38] Allopregnanolone as regenerative therapeutic for Alzheimer's disease: Translational development and clinical promise [J].

Irwin, Ronald W. ;

Brinton, Roberta Diaz .

PROGRESS IN NEUROBIOLOGY, 2014, 113 :40-55

[39] Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis [J].

Iturria-Medina, Y. ;

Sotero, R. C. ;

Toussaint, P. J. ;

Mateos-Perez, J. M. ;

Evans, A. C. .

NATURE COMMUNICATIONS, 2016, 7

[40] Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk [J].

Jansen, Iris E. ;

Savage, Jeanne E. ;

Watanabe, Kyoko ;

Bryois, Julien ;

Williams, Dylan M. ;

Steinberg, Stacy ;

Sealock, Julia ;

Karlsson, Ida K. ;

Hagg, Sara ;

Athanasiu, Lavinia ;

Voyle, Nicola ;

Proitsi, Petroula ;

Witoelar, Aree ;

Stringer, Sven ;

Aarsland, Dag ;

Almdahl, Ina S. ;

Andersen, Fred ;

Bergh, Sverre ;

Bettella, Francesco ;

Bjornsson, Sigurbjorn ;

Braekhus, Anne ;

Brathen, Geir ;

de Leeuw, Christiaan ;

Desikan, Rahul S. ;

Djurovic, Srdjan ;

Dumitrescu, Logan ;

Fladby, Tormod ;

Hohman, Timothy J. ;

Jonsson, Palmi, V ;

Kiddle, Steven J. ;

Rongve, Arvid ;

Saltvedt, Ingvild ;

Sando, Sigrid B. ;

Selbaek, Geir ;

Shoai, Maryam ;

Skene, Nathan G. ;

Snaedal, Jon ;

Stordal, Eystein ;

Ulstein, Ingun D. ;

Wang, Yunpeng ;

White, Linda R. ;

Hardy, John ;

Hjerling-Leffler, Jens ;

Sullivan, Patrick F. ;

van der Flier, Wiesje M. ;

Dobson, Richard ;

Davis, Lea K. ;

Stefansson, Hreinn ;

Stefansson, Kari ;

Pedersen, Nancy L. .

NATURE GENETICS, 2019, 51 (03) :404-+

← 1 2 3 4 5 6 7 8 9 →