Using Stems to Bear Fruit: Deciphering the Role of Alzheimer's Disease Risk Loci in Human-Induced Pluripotent Stem Cell-Derived Microglia

被引：3

作者：

Wickstead, Edward S. ^{[1
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA

来源：

BIOMEDICINES | 2023年 / 11卷 / 08期

关键词：

Alzheimer's disease; GWAS; iPSC; microglia; neurodegeneration; neuroinflammation; stem cells; MISSENSE MUTATIONS; BRAIN ORGANOIDS; MOUSE; PROTEIN; GENE; DIFFERENTIATION; NOMENCLATURE; METAANALYSIS; ACTIVATION; CHALLENGES;

D O I：

10.3390/biomedicines11082240

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease (AD) is the most common neurodegenerative disorder globally. In people aged 65 and older, it is estimated that 1 in 9 currently live with the disease. With aging being the greatest risk factor for disease onset, the physiological, social and economic burden continues to rise. Thus, AD remains a public health priority. Since 2007, genome-wide association studies (GWAS) have identified over 80 genomic loci with variants associated with increased AD risk. Although some variants are beginning to be characterized, the effects of many risk loci remain to be elucidated. One advancement which may help provide a patient-focused approach to tackle this issue is the application of gene editing technology and human-induced pluripotent stem cells (hiPSCs). The relatively non-invasive acquisition of cells from patients with known AD risk loci may provide important insights into the pathological role of these risk variants. Of the risk genes identified, many have been associated with the immune system, including ABCA7, CLU, MEF2C, PICALM and TREM2-genes known to be highly expressed in microglia. This review will detail the potential of using hiPSC-derived microglia to help clarify the role of immune-associated genetic risk variants in AD.

引用

页数：13

共 110 条

[1] iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases [J].

Abud, Edsel M. ;

Ramirez, Ricardo N. ;

Martinez, Eric S. ;

Healy, Luke M. ;

Nguyen, Cecilia H. H. ;

Newman, Sean A. ;

Yeromin, Andriy V. ;

Scarfone, Vanessa M. ;

Marsh, Samuel E. ;

Fimbres, Cristhian ;

Caraway, Chad A. ;

Fote, Gianna M. ;

Madany, Abdullah M. ;

Agrawal, Anshu ;

Kayed, Rakez ;

Gylys, Karen H. ;

Cahalan, Michael D. ;

Cummings, Brian J. ;

Antel, Jack P. ;

Mortazavi, Ali ;

Carson, Monica J. ;

Poon, Wayne W. ;

Blurton-Jones, Mathew .

NEURON, 2017, 94 (02) :278-+

[2] Evaluation of Aducanumab for Alzheimer Disease Scientific Evidence and Regulatory Review Involving Efficacy, Safety, and Futility [J].

Alexander, G. Caleb ;

Emerson, Scott ;

Kesselheim, Aaron S. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2021, 325 (17) :1717-1718

[3] Concerning unsual medical cases in old age [J].

Alzheimer, A .

ZEITSCHRIFT FUR DIE GESAMTE NEUROLOGIE UND PSYCHIATRIE, 1911, 4 :356-385

[4]

Alzheimer's Association, 2023, Alzheimer's Disease Facts and Figures 2023

[5]

Alzheimer's Disease International World Alzheimer Report, 2018, The State of the Art of Dementia Research: New Frontiers

[6] Challenges of Organoid Research [J].

Andrews, Madeline G. ;

Kriegstein, Arnold R. .

ANNUAL REVIEW OF NEUROSCIENCE, 2022, 45 :23-39

[7] The complex genetic architecture of Alzheimer?s disease: novel insights and future directions [J].

Andrews, Shea. J. ;

Renton, Alan E. ;

Fulton-Howard, Brian ;

Podlesny-Drabiniok, Anna ;

Marcora, Edoardo ;

Goate, Alison M. .

EBIOMEDICINE, 2023, 90

[8] Consensus recommendations for the postmortem diagnosis of Alzheimer's disease [J].

Ball, M ;

Braak, H ;

Coleman, P ;

Dickson, D ;

Duyckaerts, C ;

Gambetti, P ;

Hansen, L ;

Hyman, B ;

Jellinger, K ;

Markesbery, W ;

Perl, D ;

Powers, J ;

Price, J ;

Trojanowski, JQ ;

Wisniewski, H ;

Phelps, C ;

Khachaturian, Z .

NEUROBIOLOGY OF AGING, 1997, 18 (04) :S1-S2

[9] New insights into the genetic etiology of Alzheimer's disease and related dementias [J].

Bellenguez, Celine ;

Kucukali, Fahri ;

Jansen, Iris E. ;

Kleineidam, Luca ;

Moreno-Grau, Sonia ;

Amin, Najaf ;

Naj, Adam C. ;

Campos-Martin, Rafael ;

Grenier-Boley, Benjamin ;

Andrade, Victor ;

Holmans, Peter A. ;

Boland, Anne ;

Damotte, Vincent ;

van der Lee, Sven J. ;

Costa, Marcos R. ;

Kuulasmaa, Teemu ;

Yang, Qiong ;

De Rojas, Itziar ;

Bis, Joshua C. ;

Yaqub, Amber ;

Prokic, Ivana ;

Chapuis, Julien ;

Ahmad, Shahzad ;

Giedraitis, Vilmantas ;

Aarsland, Dag ;

Garcia-Gonzalez, Pablo ;

Abdelnour, Carla ;

Alarcon-Martin, Emilio ;

Alcolea, Daniel ;

Alegret, Montserrat ;

Alvarez, Ignacio ;

Alvarez, Victoria ;

Armstrong, Nicola J. ;

Tsolaki, Anthoula ;

Antunez, Carmen ;

Appollonio, Ildebrando ;

Arcaro, Marina ;

Archetti, Silvana ;

Arias Pastor, Alfonso ;

Arosio, Beatrice ;

Athanasiu, Lavinia ;

Bailly, Henri ;

Banaj, Nerisa ;

Baquero, Miquel ;

Barral, Sandra ;

Beiser, Alexa ;

Pastor, Ana Belen ;

Below, Jennifer E. ;

Benchek, Penelope ;

Benussi, Luisa .

NATURE GENETICS, 2022, 54 (04) :412-436

[10] New tools for studying microglia in the mouse and human CNS [J].

Bennett, Mariko L. ;

Bennett, F. Chris ;

Liddelow, Shane A. ;

Ajami, Bahareh ;

Zamanian, Jennifer L. ;

Fernhoff, Nathaniel B. ;

Mulinyawe, Sara B. ;

Bohlen, Christopher J. ;

Adil, Aykezar ;

Tucker, Andrew ;

Weissman, Irving L. ;

Chang, Edward F. ;

Li, Gordon ;

Grant, Gerald A. ;

Gephart, Melanie G. Hayden ;

Barres, Ben A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (12) :E1738-E1746

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