PPMI Pathology Core Tatiana Foroud & Tom Montine

Pathology Core Infrastructure Stanford University Pathology Core Indiana University Pathology Core

PPMI Pathology Core Overview Plan Brain Donation Introduction to Participant Brain Collection Neuropath Evaluation Specimen Repository

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 Pending Amend 12 approval: (19) University of South Florida, (28) JHU, (88) NWU

PPMI Subject Referrals by Arm

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

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 ClinicoPathologic 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 (6E10) IHC, Cerebellum

Anti-PHF-tau IHC; BA17

H&E/LFB; Substantia Nigra

Anti-P129 alpha-Synuclein IHC; DMN X

Anti-P129 alpha-Synuclein IHC; BA9

Anti-P129 alpha-Synuclein IHC; amygdala

PPMI Case 2018-01 High Level AD Neuropathologic Change A3, B3, C3 CAA (grade 2/3) Neocortical LB Disease DMNX, SN, anterior cingulate gyrus, BA9 Amygdala No evidence of: Microinfarcts Hippocampal sclerosis TDP-43 cytoplasmic inclusions