The Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing .

(AUSTRALIAN ADNI)

July 2015 UPDATE Christopher Rowe MD –

Neuroimaging stream leader

AIBL commenced recruitment in October 2006.

Total Recruitment to Date = 1550.

Enrichment follow-up

397 NMC 361 NMC 311 NMC 261 NMC

Inception follow-up

213 NMC 105 NMC 619 SMC 499 SMC 348 SMC 299SMC 271 SMC 141 SMC 234 MCI 139 MCI 66 MCI 51 MCI 48 MCI 17 MCI 291 AD 246 AD 170 AD 102 AD 59 AD 12 AD 5 Non-AD 5 Non-AD 6 Non-AD 5 Non-AD 7 Non-AD 4 Non-AD

Years Person years

NMC

1877

SMC

2337

MCI

483

AD

884

Non-AD

41

Total

5619 0m 18m 36m 54m 72m 90m

AIBL Highlights

AD Mean A b PET has defined the course of AD Villemagne VL, et al. Lancet Neurology 2013 - diagnostic, prognostic and therapeutic implications Continually under refinement.

Genes and lifestyle influences on decline

Lim YY et al. Molecular Psychiatry 2014

GWAS and SNP analyses underway.

Detectable

0 10 20 30 yrs

0,10 -0,40 -0,90 -1,40 -1,90 -2,40 Aβ+ ε4 Baseline l Aβ+ ε4+ BDNF Val/Va 18 month 36 month

Aβ+ ε4+ BDNF Met

54 month

4.5 year imaging data release

PiB Baseline (288), 3 years (173), 4.5 yrs (141) Plus 230 more imaged with flutemetamol, florbetapir or PiB at 3 or 4.5 yrs Plus 245 new recruits (150 flute, 95 FBP) (A b status known in 371 subjects with 4.5 yrs of follow-up) www.adni.loni.usc.edu

- Data and Samples - Access Data

Implemented the Centiloid transformation for 11 C-PiB and 18 F-NAV4694 with 18 F-Florbetapir to follow.

160 140 120 100 80 60 40 20 0 -20 0,5 1,0 1,5 2,0 GAAIN PiB SUVR 2,5 3,0

Tau Imaging

Beta-amyloid AV1451 THK5117 (now replaced with THK5351) Tau

THK5317 tau imaging in Alzheimer’s disease tau A b Braak & Braak Stage V-VI 18 F-THK5317 18 F-FLUTEMETAMOL Braak & Braak Stage C MilxView

Negative A b PET

18 F-THK5351 PET

Normal 71 yr old.

MMSE 29

.

Mild tau tracer retention in anteromedial temporal lobe but much less than in AD

A b PET +ve 69 yrs old female with MCI MMSE 24 CDR 0.5

Tau PET – right top and bottom - 18F-THK5351

64 yrs with “AD” but A b PET Negative Memory -3 SD Other domains OK MMSE 28 CDR 1 THK5351 shows high medial temporal tau

Screening for AD Drug Trials

Cumulative Stats: Dec '14- June '15

200 150 100 50 0 De ce m be r Ja nu ar y Fe br ua ry M ar ch Ap ril M ay Ju ne Referrals Screens Completers

MCI/AD Referrals to June '15

200 150 100 50 0 Total Ref Waiting Excluded Eligible Total Screens To date 9/43 (20%) had negative A b PET FDG and amyloid PET if: - MCI/mild AD (CVLT <-1 SD) - trial suitable - willing to go into a drug trial Reports go to treating doctor.

That doctor chooses trial or asks us to do this.

All scanned patients enrol in AIBL - more MCI/AD baseline data - good source of A b –ve MCI and AD mimics - (20%)

A4 Trial in Australia

Over 1000 website registrations of interest A b PET screening commenced early 2015 50 screening PET to date Aiming for 100 on study

AIBL-VETS

Tau and Beta-Amyloid Deposition, Micro hemorrhage and Brain Function after Traumatic Brain Injury in War Veterans

Award W81XWH-13-MRPRA-CSRA Principal Investigator: Christopher Rowe MD

Future Directions for AIBL

• Further refine prognostic value and comparative effectiveness of imaging and blood biomarkers • Examine genetic and environmental influences on rate of decline in A b +ve HC • Serial tau imaging • Create new pools of A b intervention trials +ve for early • Use AIBL infrastructure to support more A4 and DIAN therapy type trials

A CKNOWLEDGEMENTS AIBL study participants and their families AIBL Study team David Ames Denise El-Sheikh Mary Barnes Kevin Barnham Shayne Bellingham Maree Farrow Noel Faux Michael Fenech Sabine Bird Julia Bomke Shane Fernandez Binosha Fernando Pierrick Bourgeat Christopher Fowler Sveltana Bozinovski (nee Pejoska) Maxime Francois Jurgen Fripp Belinda Brown Shaun Frost Rachel Buckley Samantha Burnham Simon Gibson Ashley Bush Sam Gardener Veer Gupta Pratishtha Chatterjee David Hanson Karra Harrington Lesley Cheng Andy Hill Steven Collins Eugene Hone Ian Cooke Maryam Hor Kay Cox Malcolm Horne Elizabeth Cyarto Gareth Jones David Darby Adrian Kamer James Doecke Yogi Kanagasingam Vincent Dore Neil Killeen Hannah Korrel Fiona Lamb Nicola Lautenschlager Simon Laws Wayne Leifert Kate Lennon Hugo Leroux Qiao-Xin Li Yen Ying Lim Florence Lim Lucy Lim Linda Lockett Andrea Louey Kathy Lucas Lance Macaulay Lucy Mackintosh Ralph Martins Georgia Martins Paul Maruff Colin Masters Simon McBride Alissandra Mcilroy Julie Nigro Steve Pedrini Kayla Perez Kelly Pertile Tenielle Porter Stephanie Rainey Smith Carolina Restrepo Malcolm Riley Barbara Rita Cardoso Blaine Roberts Jo Robertson Mark Rodrigues Christopher Rowe Rebecca Rumble Tim Ryan Jack Sach Olivier Salvado Neil Saunders Greg Savage KaiKai Shen Brendan Silbert Harmid Sohrabi Kevin Taddei Tania Taddei Sherilyn Tan Christine Thai Philip Thomas Brett Trounson Giuseppe Verdile Victor Villemagne Irene Volitakis Michael Vovos Larry Ward Andrew Watt Mike Weinborn Rob Williams Bill Wilson Michael Woodward Paul Yates Fernanda Yevenes Ugarte Ping Zhang AIBL is a large collaborative study and a complete list of contributors can be found at www.aibl.csiro.au