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High content, multi-parameter analyses in buccal cells to identify Alzheimer's Disease
François, Maxime Fenech, Michael F. Thomas, Philip Hor, Maryam Savage, Greg Martins, Ralph N. Rainey-Smith, Stephanie R. Masters, Colin L. Ames, David Rowe, Christopher C.
François, Maxime
Fenech, Michael F.
Thomas, Philip
Hor, Maryam
Savage, Greg
Martins, Ralph N.
Rainey-Smith, Stephanie R.
Masters, Colin L.
Ames, David
Rowe, Christopher C.
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Author
François, Maxime
Fenech, Michael F.
Thomas, Philip
Hor, Maryam
Savage, Greg
Martins, Ralph N.
Rainey-Smith, Stephanie R.
Masters, Colin L.
Ames, David
Rowe, Christopher C.
Macaulay, Stuart Lance
Hill, Andrew F.
Leifert, Wayne R.
Appannah, Arti
Barnes, Margaret
Barnham, K. J.
Bedo, Justin
Bellingham, Shayne
Bon, Lynette
Bourgeat, Pierrick
Brown, Belinda M.
Buckley, Rachel F.
Burnham, Samantha
Bush, Ashley I.
Chandler, Graeme
Chen, Karren
Clarnette, Roger
Collins, Steven
Cooke, Ian
Cowie, Tiffany
Cox, Kay L.
Cuningham, Emily
Cyarto, Elizabeth V.
Dang, Phuong Anh Vu
Darby, David
Desmond, Patricia
Doecke, James D.
Dore, Vincent
Downing, Harriet
Dridan, Belinda
Duesing, Konsta
Fahey, Michael
Farrow, Maree
Faux, Noel G.
Fernandez, Shane
Fernando, Binosha
Fowler, Chris
Fripp, Jurgen
Frost, Shaun
Gardener, Samantha
Gibson, Simon
Gardener, Samantha L.
Gupta, Veer
Graham, Paula
Gupta, Veer Bala Ala
Hone, Eugene
Horne, Malcolm
Huckstepp, Brenda
Jones, Andrew
Jones, Gareth
Kamer, Adrian
Kanagasingam, Yogesan
Keam, Lisa
Kowalczyk, Adam
Krivdic, Betty
Lam, Chiou Peng
Lamb, Fiona
Lautenschlager, Nicola
Laws, Simon
Lam, Chiou Peng
Leroux, Hugo
Lautenschlager, Nicola T.
Laws, Simon M.
Lim, Florence
Lim, Lucy
Lockett, Linda
Lucas, Kathy
Mano, Mark
Marczak, Caroline
Martins, Georgia
Maruff, Paul
Matsumoto, Yumiko
Bird, Sabine
McBride, Simon J.
Szoeke, Cassandra
Fenech, Michael F.
Thomas, Philip
Hor, Maryam
Savage, Greg
Martins, Ralph N.
Rainey-Smith, Stephanie R.
Masters, Colin L.
Ames, David
Rowe, Christopher C.
Macaulay, Stuart Lance
Hill, Andrew F.
Leifert, Wayne R.
Appannah, Arti
Barnes, Margaret
Barnham, K. J.
Bedo, Justin
Bellingham, Shayne
Bon, Lynette
Bourgeat, Pierrick
Brown, Belinda M.
Buckley, Rachel F.
Burnham, Samantha
Bush, Ashley I.
Chandler, Graeme
Chen, Karren
Clarnette, Roger
Collins, Steven
Cooke, Ian
Cowie, Tiffany
Cox, Kay L.
Cuningham, Emily
Cyarto, Elizabeth V.
Dang, Phuong Anh Vu
Darby, David
Desmond, Patricia
Doecke, James D.
Dore, Vincent
Downing, Harriet
Dridan, Belinda
Duesing, Konsta
Fahey, Michael
Farrow, Maree
Faux, Noel G.
Fernandez, Shane
Fernando, Binosha
Fowler, Chris
Fripp, Jurgen
Frost, Shaun
Gardener, Samantha
Gibson, Simon
Gardener, Samantha L.
Gupta, Veer
Graham, Paula
Gupta, Veer Bala Ala
Hone, Eugene
Horne, Malcolm
Huckstepp, Brenda
Jones, Andrew
Jones, Gareth
Kamer, Adrian
Kanagasingam, Yogesan
Keam, Lisa
Kowalczyk, Adam
Krivdic, Betty
Lam, Chiou Peng
Lamb, Fiona
Lautenschlager, Nicola
Laws, Simon
Lam, Chiou Peng
Leroux, Hugo
Lautenschlager, Nicola T.
Laws, Simon M.
Lim, Florence
Lim, Lucy
Lockett, Linda
Lucas, Kathy
Mano, Mark
Marczak, Caroline
Martins, Georgia
Maruff, Paul
Matsumoto, Yumiko
Bird, Sabine
McBride, Simon J.
Szoeke, Cassandra
Abstract
Alzheimer’s disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.
Keywords
Alzheimer's disease, DNA content, amyloid, buccal cells, laser scanning cytometry, mild cognitive impairment, neutral lipids
Date
2016
Type
Journal article
Journal
Current Alzheimer Research
Book
Volume
13
Issue
7
Page Range
787-799
Article Number
ACU Department
School of Allied Health
Faculty of Health Sciences
Faculty of Health Sciences
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