1. Alzheimer’s Disease Neuroimaging Initiative Neuropathology Core John C. Morris, MD Nigel J. Cairns, PhD, FRCPath Erin Householder, MS

2. Table 1. ADNI Autopsy Rates (9-1-05 to 3-31-14) Note: The ADNI-NPC was established on 9/1/2007. ADNI Funding Period ADNI-NPCDeathsAutopsies Annual Autopsy Rate (%) 9-1-05 to 8-31-07N0600 9-1-07 to 8-31-08YES7228 9-1-08 to 8-31-09YES88100 9-1-09 to 8-31-10YES4125 9-1-10 to 8-31-11YES13646 9-1-11 to 8-31-12YES33100 9-1-12 to 8-31-13YES10880 9-1-12 to 3-31-14YES10990 Total (2005-2014)-613761 Total since NPC established-553767

3. Table 2. Brains Donated by ADNI Sites Site IDSite NameAutopsies (#) 11 Washington University School of Medicine, St. Louis7 33 University of Kansas5 23 University of Kentucky4 31 University of Texas, Southwestern MC3 24 University of Pittsburgh2 99 Banner Sun Health Research Institute2 116 University of California, Davis2 27 University of Rochester Medical College2 32 Emory University1 41 Yale University School of Medicine1 73 University of California, San Francisco1 114 Case Western Reserve University1 123 Dent Neurologic Institute1 131 Albany Medical College1 141 Rhode Island Hospital1 941 Butler Hospital Memory and Aging Program1 37 Indiana University1 29 University of California, Irvine1

4. Clinical and Demographic Data on Autopsied Cases l N = 37 l Mean Age: 81 years l Male: 81% l ε4-positive: 57% (2 cases pending) l Clinically Diagnosed –AD Dementia: 76% –MCI-amnestic:11% –Pending: 13%

5. Table 3. Clinical and Neuropathologic Diagnoses at Expiration Note: N, number of ADNI cases. AD, Alzheimer’s disease; AGD, argyrophilic grain disease; DAT, dementia of the Alzheimer type; DLB, dementia with Lewy bodies; ALB, Amygdala Lewy bodies; HS, Hippocampal sclerosis; MCI, mild cognitive impairment; TDP, TDP-43 proteinopathy in the medial temporal lobe. * One case had additional AGD. Small vessel disease (arteriolosclerosis and cerebral amyloid angiopathy) was a feature of all cases bit only one case had infarcts. Clinical diagnosis Neuropathologic diagnosis [N (%)] TOTAL (%)^ AD +DLB AD +DLB +TDP AD + DLB +TDP +AGD AD +ALB +TDP AD + AGD AD + HS + AGD AD +TDP +Infarcts AGD Pending# DAT98*1111425 (68) DAT+DLB1113 (8) MCI- Amnestic 21**14 (11) Pending^^55 (13) TOTAL (%) 11 (28) 8 (22) 2 (5) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 10 (27) 37 (100)

6. Clinical and Multimodal Biomarker Correlates of Neuropathology in 22 ADNI Cases Jon B. Toledo a *, Nigel J. Cairns b *, Xiao Da c, Kewei Chen d, Deborah Carter b, Napatkamon Ayutyanont d, Erin Householder b, Auttawut Roontiva d, Robert J Bauer d, Leslie M. Shaw a, Christos Davatzikos c, Michael W. Weiner e, Eric Reiman d, John Morris b ** and John Q. Trojanowski a **, and the Alzheimer’s Disease Neuroimaging Initiative*** a Department of Pathology & Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, b Department of Neurology, Washington University School of Medicine, St. Louis, MO, c Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, PA, d Banner Alzheimer's Institute, 901 East Willetta Street, Phoenix, AZ, e Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA. *These authors contributed equally to this paper. Acta Neuropathol. Commun. 2013;1:65

7. Participant Characteristics (n = 22) l Age = 72-88 l Gender = 77% male l Education = 13-18 y l APOE4+ = 50% l Clinically –1 CN to MCI –3 MCI stable –8 MCI to DAT –10 DAT l A clinical Dx of DAT or MCI due to AD was supported by a pathological Dx of AD in all cases l Other pathologies: TDP, SVD, DLB, AGD, HS

8. ADNI: Semi-quantitative Neuropathologic “Heat Map” Grading of ADNI Cases

9. DOD ADNI l The ADNI NP Core serves as the DOD ADNI NP Core –Cognitively normal when enrolled –No budget proposed “as few autopsies are expected during the period of the DOD grant” l DOD MCI ADNI grant also to be served by ADNI NP Core –7-1-13 through 6-30-16 –2 brain autopsies estimated/budgeted per year

10. Proposed ADNI-3: Neuropathology Core Aims l Aim 1: Foster and facilitate voluntary brain autopsy for all deceased ADNI participants l Aim 2: Provide uniform neuropathological assessments on all autopsied ADNI participants l Aim 3: Maintain a repository of frozen and fixed brain tissue from ADNI participants l Aim 4: Conduct neuropathological correlative studies with biomarkers (CSF) and imaging measures of the molecular pathology (Aβ, tau) of Alzheimer disease