Genetic Variants in Alzheimer's Disease

256 Pages·2013·5.04 MB·English

by  Kevin Morgan

Kevin Morgan · Minerva M. Carrasquillo
Editors
Genetic
Variants in
Alzheimer's
Disease
Genetic Variants in Alzheimer’s Disease

Kevin Morgan (cid:129) Minerva M. Carrasquillo

Editors
Genetic Variants
in Alzheimer’s Disease
Editors
Kevin Morgan Minerva M. Carrasquillo
School of Molecular Medical Sciences Department of Neuroscience
Queen’s Medical Centre Mayo Clinic College of Medicine
University of Nottingham Jacksonville , FL, USA
Nottingham , UK
ISBN 978-1-4614-7308-4 ISBN 978-1-4614-7309-1 (eBook)
DOI 10.1007/978-1-4614-7309-1
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2013940606
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Contents
1 The Genetics of Alzheimer’s Disease:
Introduction and Perspective for the Future ....................................... 1
Kevin Morgan and Minerva M. Carrasquillo
2 Apolipoprotein E .................................................................................... 7
Minerva M. Carrasquillo, Guojun Bu, and Henrietta M. Nielsen
3 Clusterin.................................................................................................. 25
Jenny Lord and Kevin Morgan
4 PICALM ................................................................................................. 53
Jenny Lord and Kevin Morgan
5 Complement Component (3b/4b) Receptor 1 (CR1) ........................... 77
Jenny Lord and Kevin Morgan
6 Bridging Integrator 1 (BIN1) ................................................................ 103
James Turton and Kevin Morgan
7 ATP-Binding Cassette, Subfamily A (ABC1), Member 7 (ABCA7) ... 135
James Turton and Kevin Morgan
8 Membrane-Spanning 4-Domains Subfamily A, MS4A Cluster ......... 159
Kristelle Brown, James Turton, and Kevin Morgan
9 Sialic Acid Binding Immunoglobulin-Like Lectin-3 (CD33).............. 181
Christopher Medway and Kevin Morgan
10 Erythropoietin-Producing Human Hepatocellular
Carcinoma (EphA1) ............................................................................... 191
Christopher Medway, Anne Braae, and Kevin Morgan
11 CD2-Associated Protein (CD2AP) ........................................................ 201
Christopher Medway and Kevin Morgan
vv
vi Contents
12 Other Genes Implicated in Alzheimer’s Disease ................................. 209
Minerva M. Carrasquillo, Mariet Allen, and Nilüfer Ertekin-Taner
13 The Future Role of Biomarkers in Alzheimer’s
Disease Diagnostics ................................................................................ 231
Joanna L. Richens, Bharak Vafadar-Isfahani, Kelly-Ann Vere,
Graham Ball, Noor Kalsheker, Robert Rees, Nin Bajaj, Paul O’Shea,
and Kevin Morgan
Index ................................................................................................................ 249
Contributors
Mariet Allen Department of Neuroscience , Mayo Clinic College of Medicine ,
Jacksonville , FL , USA
Nin Bajaj Department of Neurology, Queen’s Medical Centre, Nottingham
University Hospitals NHS Trust , Nottingham , UK
Graham Ball The John van Geest Cancer Research Centre, School of Science and
Technology, Nottingham Trent University , Nottingham , UK
Anne Braae Human Genetics, School of Molecular Medical Sciences, Queen’s
Medical Centre , University of Nottingham , Nottingham , UK
Kristelle Brown Human Genetics, School of Molecular Medical Sciences, Queen’s
Medical Centre , University of Nottingham , Nottingham , UK
Guojun B u Department of Neuroscience , Mayo Clinic College of Medicine ,
Jacksonville , FL , USA
Minerva M. Carrasquillo Department of Neuroscience , Mayo Clinic College of
Medicine , Jacksonville , FL , USA
Nilüfer Ertekin-Taner Departments of Neurology and Neuroscience , Mayo
Clinic College of Medicine , Jacksonville , FL , USA
Noor Kalsheker Human Genetics, School of Molecular Medical Sciences,
Queen’s Medical Centre , University of Nottingham , Nottingham , UK
Jenny Lord Human Genetics, School of Molecular Medical Sciences, Queen’s
Medical Centre , University of Nottingham , Nottingham , UK
Christopher Medway Human Genetics, School of Molecular Medical Sciences,
Queen’s Medical Centre , University of Nottingham , Nottingham , UK
Kevin Morgan Human Genetics, School of Molecular Medical Sciences, Queen’s
Medical Centre , University of Nottingham , Nottingham , UK
vviiii
viii Contributors
Henrietta M. Nielsen Department of Neuroscience , Mayo Clinic College of
Medicine , Jacksonville , FL , USA
Paul O’Shea Cell Biophysics Group, Institute of Biophysics, Imaging and Optical
Science, School of Biology, University of Nottingham , Nottingham , UK
Robert Rees The John van Geest Cancer Research Centre, School of Science and
Technology, Nottingham Trent University , Nottingham , UK
Joanna L. Richens Cell Biophysics Group, Institute of Biophysics, Imaging and
Optical Science, School of Biology, University of Nottingham , Nottingham , UK
James Turton Human Genetics, School of Molecular Medical Sciences, Queen’s
Medical Centre , University of Nottingham , Nottingham , UK
Bharak Vafadar-Isfahani The John van Geest Cancer Research Centre, School of
Science and Technology, Nottingham Trent University , Nottingham , UK
Kelly-Ann Vere Cell Biophysics Group, Institute of Biophysics, Imaging and
Optical Science, School of Biology, University of Nottingham , Nottingham , UK
Chapter 1
The Genetics of Alzheimer’s Disease:
Introduction and Perspective for the Future
Kevin Morgan and Minerva M. Carrasquillo
It is evident that since late 2009 our understanding of the genetics of Alzheimer’s
disease (AD) has increased immeasurably as to date nine new genes associated with
AD have been identifi ed through genome-wide association studies (GWAS) [1 – 5 ].
These genes are C LU —clusterin, PICALM —phosphatidylinositol-binding clathrin
assembly protein, CR1 —complement receptor 1, B IN1 —bridging integrator 1,
ABCA7 —ATP-binding cassette transporter, subfamily A (ABC1), member 7, M S4A
cluster—membrane-spanning 4-domains subfamily A, C D2AP —CD2-associated
protein, C D33 —sialic-acid binding immunoglobulin-like lectin and EPHA1 —
ephrin receptor 1. Strictly speaking we should say nine new genetic loci as in most
instances the index SNP (single nucleotide polymorphism) identifi ed by GWAS is
not directly located in exonic coding sequence and in these instances the nearest
gene has been ‘nominated’. In fact, the index SNPs normally ‘tag’ large regions of
sequence (linkage blocks) and conceptually any gene within these blocks could be
the ‘culprit’. More recently, two independent next generation sequencing (NGS)
genome and exome sequencing screens identifi ed a tenth AD risk locus, which har-
bours coding variants in TREM2 (triggering receptor expressed on myeloid cells 2)
gene [6 , 7 ].
Prior to this, for 20 years, the only replicable genetic factor associated with late-
onset AD was the A POE 4 allele [8 ] and since this observation represented the
‘birth’ of late-onset AD genetics, this book begins with a chapter devoted to this
gene. Likewise, each of the nine new GWAS genes/loci has a chapter solely dedi-
cated to it. TREM2 is more briefl y discussed in the last chapter, along with genes
identifi ed using approaches other than GWAS.
K. Morgan (*)
Human Genetics, School of Molecular Medical Sciences, Queen’s Medical Centre ,
University of Nottingham , Nottingham NG7 2UH , UK
e-mail: [email protected]
M. M. Carrasquillo
Department of Neuroscience , Mayo Clinic College of Medicine ,
4500 San Pablo Road, Jacksonville , FL 32224 , USA
K. Morgan and M.M. Carrasquillo (eds.), Genetic Variants in Alzheimer’s Disease, 1
DOI 10.1007/978-1-4614-7309-1_1, © Springer Science+Business Media New York 2013