PPMI PATHOLOGY CORE TATIANA FOROUD TOM MONTINE Pathology

PPMI PATHOLOGY CORE TATIANA FOROUD & TOM MONTINE

Pathology Core Infrastructure Stanford University Pathology Core Indiana University Pathology Core

PPMI PATHOLOGY CORE OVERVIEW Introduction to Participant Plan Brain Donation Brain Collection Neuropath Evaluation Specimen Repository 3

Site Coordinators are the Key! • Provide talking points for site coordinators and stress their important role in helping with engagement – Contribution to understanding PD progression – No additional cost to subject – Post mortem report provided to family

Pathology Core Referral

PPMI Site Referrals to Pathology Core 0 0 0 13 52 12 23 17 Site (96) Seattle (12) Parkinson's Institute (196) Boca Raton (86) Beth Israel (73) UCSF (7) Baylor (6) Oregon (57) UAB (40) Boston (34) IND (32) Emory (23) UCSD (2) Columbia (18) U Penn (154) Banner (120) Cleveland (1) Rochester 31 150 7 4 1 38 8 9 2 0 20 40 60 80 Subject Count 100 120 Pending Amend 12 approval: (19) University of South Florida, (28) JHU, (88) NWU 140 160

PPMI Subject Referrals by Arm. . . 5 2 . . . 11 5 . . . 64 21 . . . 18 9 . . . 12 5 . . . 1 4 . . . 91 56 . . . 28 0 10 20 30 35 40 50 Incomplete 60 Complete 70 80 90 100

PPMI Pathology Core Update PPMI Site Referral to PPMI Path Core (n=367) PPMI Path Core: Contacts Subject, explains Core (n= 367) Decline/lost to f-up (n=54) Subject sent IC and CRF (paper/electronic) (n=245) Completed IC and CRF received (n=135) Brain removal plan in place and documented (n=127) Not yet successfully contacted (n=52) & Request delayed planning (n=16) IC pending completion; reminder sent every 3 weeks (n=110) Still planning (n=8)

Planning Challenges • Finding removal specialists with 24/7 coverage to help with <8 hr removal goals • Coordinating donations for subjects enrolled in multiple donations programs • Identifying subjects who might have already donated to other brain banks

Brain Donation • Three PPMI subjects have samples at Stanford University – One individual was planned by PPMI Pathology Core and brain was successfully obtained – Two individuals had planned for donation prior to the establishment of the PPMI Pathology Core • Tissue/slides from recipient brain banks transferred to Stanford – Preliminary evaluation of one case completed • Clinico. Pathologic Case (CPC) conference to be scheduled

Goals for the Coming Year • Annual confirmation with PPMI participants who have a plan in place • Continue to receive referrals from US PPMI sites • European and International PPMI site expansion – Establish harmonized IHC staining protocol across international sites – Neuropathology evaluation to be performed at either international site with data transfer to Stanford or at Stanford • Finalize plans for data transfer with LONI – Pathology slide images (Stanford University) – Pathology specimen catalog (Indiana University)

Case 2018 -01 • 80 yo woman with history of movement disorder and cognitive impairment • Brain – 1370 gm – Mild cerebral cortical atrophy – Enlarged lateral ventricles – Moderate atrophy of hippocampus – Moderate pallor of SN and LC

Anti-Amyloid B (6 E 10) IHC, Cerebellum

Anti-PHF-tau IHC; BA 17

H&E/LFB; Substantia Nigra

Anti-P 129 alpha-Synuclein IHC; DMN X

Anti-P 129 alpha-Synuclein IHC; BA 9

Anti-P 129 alpha-Synuclein IHC; amygdala

PPMI Case 2018 -01 • High Level AD Neuropathologic Change – A 3, B 3, C 3 – CAA (grade 2/3) • Neocortical LB Disease – DMNX, SN, anterior cingulate gyrus, BA 9 – Amygdala • No evidence of: – Microinfarcts – Hippocampal sclerosis – TDP-43 cytoplasmic inclusions