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Alzheimer’s Disease: Insights from Genetic Mouse Models and Current Advances in Human IPSC-Derived Neurons

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Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 15))

Abstract

Alzheimer’s disease was first described in 1906 and since then tremendous efforts have been made to fully understand the disease pathology and to find a cure for this neurodegenerative disease. The diagnosis of Alzheimer’s is still difficult, especially in early stages of the disease. Current treatment of Alzheimer’s only ameliorates the symptoms but fails to provide a therapy. Over the last decades, animal models have been proven valuable in elucidating insights of the pathology. In vitro models using patient-derived cells are currently emerging and hold great promise in understanding the disease pathophysiology. Here, we introduce the neurobiology and genetic features of Alzheimer’s and describe what we have learned from studies employing mouse models and patient-derived induced pluripotent stem cells.

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Abbreviations

3D:

Three-dimensional

ABAD:

Aß-binding alcohol dehydrogenase

AD:

Alzheimer’s disease

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

ApoE:

Apolipoprotein E

APP:

Amyloid precursor protein

ATP:

Adenosine triphosphate

Aβ:

Amyloid-β

BDNF:

Brain-derived neurotropic factor

BiP:

Binding immunoglobulin protein

cAMP:

Cyclic adenosine monophosphate

cdk5:

Cyclin-dependent kinase

CHOP:

CCAAT-enhancer-binding protein homologous protein

CRISPR:

Clustered regularly interspaced palindromic repeats

CSF:

Cerebrospinal fluid

CT:

Computed tomography

CTF83:

Carboxy-terminal fragment produced by the α-secretase

CTF99:

Carboxy-terminal fragment produced by the β-secretase

DS:

Down syndrome

FAD:

Familial AD

FTD:

Frontotemporal dementia

GSI:

β-Secretase inhibitor

GSK3β:

Glycogen synthase kinase 3β

GSM:

β-Secretase modulator

hiPSCs:

Human induced pluripotent stem cells

htau:

Human tau

IPSCs:

Induced pluripotent stem cells

MAPT:

Microtubule-associated protein tau

MB:

Methylene blue

miRNA:

Micro RNA

MRI:

Magnetic resonance imaging

mRNA:

Messenger RNA

NFTs:

Neurofibrillary tangles

NMDARs:

N-methyl-d-aspartate receptors

NO:

Nitric oxide

NR1:

NMDAR subunit 1

NR2A-NR2D:

NMDAR subunit 2A-D

NR3A-NR2B:

NMDAR subunit 3A-B

PDGF:

Platelet-derived growth factor

PET:

Positron emission tomography

PIB:

Pittsburgh Compound-B

PP2A:

Protein phosphatase 2A

PrPC:

Cellular prion protein

PSD95:

Postsynaptic density protein 95

PSEN:

Presenilin protein

RNA:

Ribonucleic acid

ROS:

Reactive oxidative species

SAD:

Sporadic AD

sAPPα/sAPPβ:

Soluble extracellular APP fragment after α- or β-secretase processing, respectively

shRNA:

Short hairpin RNA

SNP:

Single-nucleotide polymorphism

ZFNs:

Zinc-finger nucleases

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Acknowledgements

This work has been supported by funding from the National Health & Medical Research Council (#1081916, #1037746, #1003083) and the Australian Research Council (#DP130102027).

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Authors and Affiliations

  1. Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, NSW, 2052, Australia

    Anne E. Harasta Ph.D. & Lars M. Ittner M.D.

  2. Transgenic Animal Unit, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW, 2052, Australia

    Lars M. Ittner M.D.

  3. Neuroscience Research Australia, Sydney, NSW, 2037, Australia

    Lars M. Ittner M.D.

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  1. Anne E. Harasta Ph.D.
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Correspondence to Anne E. Harasta Ph.D. .

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Editors and Affiliations

  1. University of Melbourne Florey Institute of Neuroscience and Mental Health, Parkville, Australia

    Philip Beart

  2. Pediatrics and Pharmacology Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Michael Robinson

  3. School of Life Sciences Bradford School of Pharmacy, University of Bradford, Bradford, United Kingdom

    Marcus Rattray

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Nicholas J. Maragakis

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Harasta, A.E., Ittner, L.M. (2017). Alzheimer’s Disease: Insights from Genetic Mouse Models and Current Advances in Human IPSC-Derived Neurons. In: Beart, P., Robinson, M., Rattray, M., Maragakis, N. (eds) Neurodegenerative Diseases. Advances in Neurobiology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-57193-5_1

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