PPMI PATHOLOGY CORETATIANA FOROUD &

TOM MONTINE

Pathology Core Infrastructure

Indiana University Pathology Core

Stanford University Pathology Core

3

PPMI PATHOLOGY CORE OVERVIEW

Plan Brain Donation

Introduction to Participant

Brain Collection

NeuropathEvaluation

SpecimenRepository

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

2

9

8

38

1

4

7

150

31

17

23

12

52

13

0

0

0

0 20 40 60 80 100 120 140 160

(1) Rochester(120) Cleveland

(154) Banner(18) U Penn(2) Columbia

(23) UCSD(32) Emory

(34) IND(40) Boston

(57) UAB(6) Oregon(7) Baylor(73) UCSF

(86) Beth Israel(196) Boca Raton

(12) Parkinson's Institute(96) Seattle

Subject Count

Site

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

PPMI Subject Referrals by Arm

28

56

1

5

9

21

5

2

35

91

4

12

18

64

11

5

0 10 20 30 40 50 60 70 80 90 100

Genetic Cohort PD

Genetic Cohort Unaffected

Genetic Registry PD

Genetic Registry Unaffected

HC

PD

Prodromal

SWEDD

Incomplete Complete

PPMI Pathology Core UpdatePPMI 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)

Completed IC and CRF received (n=135)

IC pending completion; reminder sent every 3

weeks (n=110)

Brain removal plan in place and documented(n=127)

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• 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