1. Update and Thank you to participants Bradley Hyman MD PhD Director, Mass ADRC ViceChair, Neurology, Massachusetts General Hospital

2. HABS turns 5 and the Mass ADRC turns 30! One of the three oldest Centers of Excellence in the country – our data combined with other Centers leads to >10,000 individuals actively enrolled in studies

3. What have we learned? What causes age related memory problems or neurodegenerative diseases? – Genes! Alzgene.org 20 new genetic risk factors – many discovered at MGH – Risk factors! Alzrisk.org Primary studies and reviews of the day to day factors that might impact your chance of having memory problems or dementia – Natural history and early changes New definition of the disease from neuropathological studies and new imaging studies – mainly from the ADRC.

4. What were important questions 25 years ago? Why do patients have memory problems as they age? Why do some people get AD, and others don’t? What goes wrong in the AD brain? How can we treat or prevent AD?

5. The lesions and genes affecting the Alzheimer Brain Tau tangles form Amyloid plaques form Neurons die Inherited genes predispose

6. Natural history Clinical diagnosis Ingelsson et al New understanding of disease led to new definitions from international working groups led in part by Drs Hyman, Sperling, Frosch and Blacker in 2012 and 2013

7. 18F T807 SUVR 2.0 1.0 70 y/o MCI MMSE = 28 PiB (mcDVR) = 1.53 2.0 1.4 SUVR AT8 Histochemistry T807 binding represents tangles Braak 2006 Keith Johnson, 2014

8. Early diagnosis and new therapies Early changes in amyloid, tau, and behaviors such as the sense of smell precede and to some extent anticipate cognitive deterioration. Early diagnosis – even presymptomatic diagnosis – might lead to a window where we can intervene. The A4 trial – led by Dr Sperling and Rentz

9. New projects pushing the frontiers of science Can we see the loss of neurons with a new generation of MRI scanner? - Dr Trey Hedden Why are some people resilient to disease? - Dr Teresa Gomez Isla Can we create better animal models of disease? Dr Brad Hyman

10. It’s a great partnership! Thank you!!!!!