1. The Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing (AUSTRALIAN ADNI). July 2015 UPDATE Christopher Rowe MD – Neuroimaging stream leader

2. 619 SMC 234 MCI 291 AD 397 NMC 5 Non-AD Person years NMCSMCMCIADNon-ADTotal Years 18772337483884415619 499 SMC 139 MCI 246 AD 361 NMC 5 Non-AD 348 SMC 66 MCI 170 AD 311 NMC 6 Non-AD 299SMC299SMC 51 MCI 102 AD 261 NMC 5 Non-AD 141 SMC 17 MCI 12 AD 105 NMC 4 Non-AD 271 SMC 48 MCI 59 AD 213 NMC 7 Non-AD Enrichment follow-up Inception follow-up AIBL commenced recruitment in October 2006. Total Recruitment to Date = 1550. 0m 18m 36m 54m 72m 90m

3. AIBL Highlights A  PET has defined the course of AD yrs 0102030 Detectable AD Mean Villemagne VL, et al. Lancet Neurology 2013 - diagnostic, prognostic and therapeutic implications Aβ+ ε4- Aβ+ ε4+ BDNF Val/Va l Aβ+ ε4+ BDNF Met Genes and lifestyle influences on decline Lim YY et al. Molecular Psychiatry 2014 Continually under refinement. GWAS and SNP analyses underway.

4. 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) www.adni.loni.usc.edu - Data and Samples - Access Data (A  status known in 371 subjects with 4.5 yrs of follow-up)

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

7. THK5117 (now replaced with THK5351) Beta-amyloidTau Tau Imaging AV1451

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

9. 18 F-THK5351 PET Normal 71 yr old. MMSE 29. Mild tau tracer retention in anteromedial temporal lobe but much less than in AD Negative A  PET

10. 69 yrs old female with MCI MMSE 24 CDR 0.5 A  PET +ve Tau PET – right top and bottom - 18F-THK5351

11. 64 yrs with “AD” but A  PET Negative Memory -3 SD Other domains OK MMSE 28 CDR 1 THK5351 shows high medial temporal tau

12. Screening for AD Drug Trials 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  –ve MCI and AD mimics - (20%) To date 9/43 (20%) had negative A  PET

13. A4 Trial in Australia Over 1000 website registrations of interest A  PET screening commenced early 2015 50 screening PET to date Aiming for 100 on study

14. Award W81XWH-13-MRPRA-CSRA Principal Investigator: Christopher Rowe MD AIBL-VETS Tau and Beta-Amyloid Deposition, Micro hemorrhage and Brain Function after Traumatic Brain Injury in War Veterans

15. 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  +ve HC Serial tau imaging Create new pools of A  +ve for early intervention trials Use AIBL infrastructure to support more A4 and DIAN therapy type trials

16. David Ames Mary Barnes Kevin Barnham Shayne Bellingham Sabine Bird Julia Bomke Pierrick Bourgeat Sveltana Bozinovski (nee Pejoska) Belinda Brown Rachel Buckley Samantha Burnham Ashley Bush Pratishtha Chatterjee Lesley Cheng Steven Collins Ian Cooke Kay Cox Elizabeth Cyarto David Darby James Doecke Vincent Dore Denise El-Sheikh Maree Farrow Noel Faux Michael Fenech Shane Fernandez Binosha Fernando Christopher Fowler Maxime Francois Jurgen Fripp Shaun Frost Sam Gardener Simon Gibson Veer Gupta David Hanson Karra Harrington Andy Hill Eugene Hone Maryam Hor Malcolm Horne Gareth Jones Adrian Kamer Yogi Kanagasingam 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 A CKNOWLEDGEMENTS AIBL study participants and their families AIBL Study team AIBL is a large collaborative study and a complete list of contributors can be found at www.aibl.csiro.au www.aibl.csiro.au