Alzheimer Disease Laboratory
We are interested in the physical basis of neurodegeneration in human brains with special concerns for Parkinson’s and Alzheimer’s related diseases. Our laboratory has three complementary lines of research:
- Neuropathology and Neurobiology
- Oxidative Stress and Neuroprotection
Each consists of multiple specific question focused projects. All our projects are centred on perceptions of interests and importance to neurodegenerative mechanisms, drawn primarily from in-house anatomical and chemical examinations of post-mortem human brain material of patients who died from Parkinson, Alzheimer or other neurodegenerative diseases obtained through the South Australian Brain Bank and Australian Tissue Bank Consortium. The South Australian Brain Bank also runs the South Australian Brain Tissue Donor Program and is executed by Ms Robyn Flook based at Flinders Medical Centre.
Neuropathology / Neurobiology: We have a long standing interest in systematically documenting cellular and subcellular pathologies in brains of Parkinson’s, Alzheimer’s and other neurodegenerative diseases. We use a range of immunological labelling (immunohistology, immunoblotting) and detecting (light, electron, atomic force imaging) techniques combined with molecular markers for generic or specific biological and pathogenic processes relevant to neurodegeneration, for example, alpha-synuclein for Lewy bodies and related pathologies in Parkinson’s disease, beta-amyloid and tau proteins for Alzheimer’s disease specific pathologies. In parallel, we use various in vitro systems (isolated proteins, cell organelles, cell cultures) to replicate aspects of pathologies observed in diseased human brains as models, to test derived hypotheses or dissect key steps of biological or cellular processes perceived to play a role in neurodegeneration in the disease.
Neuroproteomics: We isolate disease specific abnormal proteins, protein complexes or inclusion bodies from brain tissues with various neurodegenerative diseases (Lewy bodies of Parkinson’s disease, oligodendroglial inclusions of multiple system atrophy, ubiquitinated proteins in aged brain) and identify the physical nature of the abnormalities and characterize their potential role in disease pathogensis, their value for diagnosis, treatment and prevention of neurodegenerative diseases. We currently focus on establishing and developing alpha-synuclein based diagnostics for Parkinson’s and related diseases.
Oxidative Stress / Neuroprotection: We are mapping the cellular distribution of the peroxiredoxin family and other antioxidant enzymes in the human brain and determining their association with Parkinson's and Alzheimer's disease pathology. We have also isolated a GPx/alpha-synuclein aggregation isolated from Parkinson's disease brain tissue and are determining if this is either chaperone mediated autophagy or endoplasmic reticulum trafficking vesicles from the endoplasmic reticulum to the Golgi apparatus. This is a significant finding as this could indicate how Lewy bodies form or give incite into a mechanism of Lewy body degradation. We are also determining the specific pattern of toxic and oxidative damage in human brain tissue using oxidative stress biomarkers and determining if this can be replicated in a human neuronal cell. Using this same model we determining if these toxic insults result the upregulation of cellular antioxidant enzymes.
Neuropathology / Neurobiology: Wei Ping Gai, MB, MSc, PhD
Neuroproteomics: Tim Chataway, BSc(Hons), PhD
Oxidative Stress / Neuroprotection: John Power, BSc(Hons), PhD
Visiting Research Fellows / Scholar
Dr Feng Guo, PhD, China
Fariba Chegini, BSc(Hons), Research Assistant
Neuropathology / Neurobiology;
Prof Heiko Braak, Dept of Clinical Neuroanatomy,
The JW Goethe University, Frankfurt, Germany: Human Brain
Anatomy and Pathology.
Prof Poul Henning Jensen, Dept of Medical Biochemistry, Universe
of Aarhus, Denmark: Alpha-Synuclein-Interacting
Proteins in Neurogenerative Disease.
Assoc Prof Michael Schlossmacher, Division of Neurosciences, Ottawa
Health Research Institute, University of Ottawa, Canada: Proteins
associated with Lewy body disease.
Dr Jenny Hardingham and Georgia
Molecular Oncology Laboratory, Queen Elizabeth Hospital: Discovery
of biomarkers for Colorectal Cancer using Proteomic methodology.
Assoc Prof Rob Richards and Alex
Molecular Biosciences, University of Adelaide: Identifying
the function of the WWOX gene in Drosophila through Proteomic
analysis of WWOX gene knockouts.
Michael Wiese (Royal Hobart Hospital), Prof
Bob Heddle (Flinders
University), Assoc Prof Simon Brown (University
of WA) and Robert
Milne (University of South Australia): Characterisation
of ant venom proteins in Myrmecia pilosula (Jack Jumper) ant
Assoc Prof Jamie Craig, Dr Shiwani
Sharma and Dr Alex Hewitt,
Ophthalmology, Flinders University: Identification
of the molecular basis of congenital cataract formation.
Prof Keryn Williams, Dr
Helen Brereton and Mr Rhys Fogarty,
Ophthalmology, Flinders University: Heritable influences
in an animal model of retinopathy of prematurity.
Oxidative Stress / Neuroprotection:
Prof Peter Blumbergs (Dept
of Neuropathology, IMVS Adelaide) and Dr
Håkan Muyderman (Medical Biochemistry,
Flinders University): The
mechanisms of neurodegeneration and cellular antioxidant responses
in Parkinson's and Alzheimer's diseases.
Dr Sonja Klebe, Dept of Anatomical Pathology, Flinders Medical
Centre: Distribution of antioxidant enzymes in the human
eye and their association with eye diseases.
a-Synuclein in Health and Disease 2008
Systems BioMedicine of Parkinson's Disease Workshop - July 2007 (opens in new window as .pdf)
Selected Recent Publications
Majd S, Chegini F, Chataway T, Zhou XF, Gai W (2013) Reciprocal induction between α-synuclein and β-amyloid in adult rat neurons. Neurotox Res, 23(1):69-78
Zhou J, Broe M, Huang Y, Anderson JP, Gai WP, Milward EA, Porritt M, Howells D, Hughes AJ, Wang X, Halliday GM (2011) Changes in the solubility and phosphorylation of alpha-synuclein over the course of Parkinson's disease. Acta Neuropathol, 121(6):695-704
Pountney DL, Dickson TC, Power JH, Vickers JC, West AJ, Gai WP (2011) Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy. Neurotox Res, 19(1): 115-22
Wilson A, Carati C, Gannon B, Haberberger R, Chataway T (2010) Aquaporin-1 in rat circumventricular organ blood vessels. Cell and Tissue Research 340: 159-168
Wang YJ, Valadares D, Sun Y, Wang X, Zhong JH, Liu XH, Majd S, Chen L, Gao CY, Chen S, Lim Y, Pollard A, Aguilar E, Gai WP, Yang M, Zhou XF (2010) Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism. Neurotox Res, 17(3): 257-67
Seidel K, Schöls L, Nuber S, Petrasch-Parwez E, Gierga K, Wszolek Z, Dickson D, Gai WP, Bornemann A, Riess O, Rami A, Den Dunnen WF, Deller T, Rüb U, Krüger R (2010) First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Ann Neurol, 67(5):684-9. Erratum in: Ann Neurol, 67(6): 841
Paleologou KE, Oueslati A, Shakked G, Rospigliosi CC, Kim HY, Lamberto GR, Fernandez CO, Schmid A, Chegini F, Gai WP, Chiappe D, Moniatte M, Schneider BL, Aebischer P, Eliezer D, Zweckstetter M, Masliah E, Lashuel HA (2010) Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci, 30(9): 3184-98
Kragh CL, Lund LB, Febbraro F, Hansen HD, Gai W, El-Agnaf O,
Richter-Landsberg C & Jensen P (2009) Alpha-synuclein aggregation
and ser-129 phosphorylation-dependent cell death in oligodendroglial
cells. Journal of Biological Chemistry, 284(15): 10211-10222
Power JH & Blumbergs PC (2009) Cellular glutathione peroxidase
in human brain: cellular distribution, and its potential role
in the degradation of Lewy bodies in Parkinson's disease and
dementia with Lewy bodies. Acta Neuropathologica, 117(1):
Power JHT & Blumbergs PC (2009)
Glutathione peroxidase in human brain: cellular distribution
and its potential role in the degradation of Lewy bodies in Parkinson's
disease and dementia with Lewy bodies. Acta Neuropathologica 117:
Sharma S, Chataway TK, Burdon KP, Jonavicius
L, Klebe S, Hewitt AW, Mills RA & Craig J (2009)
Identification of LOXL1 protein and Apolipoprotein E as components
of surgically isolated pseudoexfoliation material by direct mass
spectrometry. Experimental Eye Research, 89(4): 479-485
Lee J, Lee I, Choe Y, Kang S, Kim HY, Gai W, Hahn J & Paik
SR (2009) Real-time analysis of amyloid fibril formation of alpha-synuclein
using a fibrillation-state-specific fluorescent probe of JC-1. Biochemical
Journal, 418(2): 311-323
Waldvogel H, Baer K, Gai W, Gilbert R, Rees M, Mohler H, Faull
RL (2008) Differential localisation of GABAA receptor subunits
within the substantia nigra of the human brain: an immunohistochemical
study. Journal of Comparative Neurology, 506: 912-929
Pountney DL, Raftery MJ, Chegini F, Blumbergs PC, Gai WP (2008)
NSF, Unc-18-1 (rbSEC1), Dynamin-1 and HSP90 are components of nuclear
inclusion bodies linked to SUMO-1. Acta Neuropathologica, 116(6): 603-14
Kirik D, Gai WP, Jensen PH (2008) Is alpha-synuclein the culprit
of the Parkinsonian neurodegeneration? Experimental Neurology, 209: 3-4
Huang Y, Song YJ, Murphy K, Holton JL, Lashley T, Revesz T, Gai
WP, Halliday GM (2008) LRRK2 and parkin immunoreactivity in multiple
system atrophy inclusions. Acta Neuropathol, 116(6): 639-46
Power JHT, Asad SK, Chataway TK, Chegini F, Manavis J, Temlett
JA, Jensen PJ, Blumbergs PC, Gai WP (2008) Peroxiredoxin 6 in human
brain: molecular forms, cellular distribution and association with
Alzheimer's disease pathology. Acta Neuropathologica, 115(6): 611-22
Lee JO, Lee IH, Choe YJ, Kang S, Hui Kim HY, Gai WP, Hahn JS, Paik
SR (2008) Real-time analysis of amyloid fibril formation of alpha-synuclein
with a fibrillation state-specific fluorescent probe of JC-1. Biochemical
Journal, 418(2): 311-323