Alzheimer's disease biomarkers

An essential requirement for clinical trials; the need for datasharing

Adapted from Sperling et al (2011) Alzheimer’s and dementia 7 280-92

Trials are conducted too late

Adapted from Sperling et al (2011) Alzheimer’s and dementia 7 280-92

Biomarkers for secondary prevention

Stratification markers

Progression markers

Biomarkers for dementia – CSF Ab and tau; PET amyloid ligands

Biomarkers and preventative trials in AD; a proposal

Stratification markers

Progression markers

High specificity, high intervention markers

e.g. CSF or PET markers of pathology

Best combination of markers

e.g. slope measurement in as short a time frame as possible

High sensitivity, low intervention markers

e.g. blood based markers discovered by targeted

endophenotype design

Unbiased, data-driven discovery

e.g. wide range of assessments; short assessment period

Biomarkers for dementia – alternative approaches

-

Albumin

Automated regional analysis of structure

AD subjects, the color represents thickness in mm.

Blue <1 mm and red=5 mm

Atlas defined on

template brain, in

stereotaxic

space“Louis Collins”

Association between inflammatory proteins levels measured in

plasma versus ventricular volume.

Leung R, Proitsi P, Simmons A, Lunnon K, et al. (2013)

Inflammatory Proteins in Plasma Are Associated with

Severity of Alzheimer’s Disease. PLoS ONE 8(6):

e64971. doi:10.1371/journal.pone.0064971

http://www.plosone.org/article/info:doi/10.1371/journal.p

one.0064971

NA-ADNI

J-ADNI

WW-ADNI

AIBL

C-ADNI AddNeuroMed

EMIF Project Vision

To enable and conduct novel research into human

health by utilising human health data at an

unprecedented scale

• Access to information on 40 million patients

• AD research on 10-times more subjects than ADNI

• Metabolics research on > 20,000 obese & T2DM subjects

• Linkage of clinical and omics data

• Development of a secure (privacy, legal) modular platform

• Continue to build a network of data sources and relevant research

EMIF – platform for modular extension

EM

IF -

Me

tab

olic

EM

IF -

AD

Data Privacy

Analytical tools

Semantic Integration

Information standards

Data access / mgmt

IMI Structure and Network

Research Topics

EMIF governance

Pre

ven

tio

n a

lgo

rith

ms

Pre

dic

tiv

e s

cre

en

ing

Ris

k s

trati

ficati

on

Call 5 Call 5

Ris

k f

acto

r an

aly

sis

Pati

en

t g

en

era

ted

data

TBD

EM

IF -

Pla

tfo

rm

Metabolic CNS

User

admin

User

admin

User

admin

TTP

TTP

TTP

Q

Q

Q

R

R

R

archive

archive

archive

EMIF systems view

User

Remote

user 1

Remote

user 2

Remote

user 3 cohorts

Site

1

Site

2

Site

3

Transactional

environment

Local EMIF solution Cloud-based EMIF solution

Security

Infrastructure

Transient

data-pool

Analytical

tools

Data

access

Module

Data

access

Module

Data

access

Module

Data

access

Module

Data

access

Module

Com

mo

n o

nto

logy

Com

mo

n o

nto

logy

Co

mm

on o

nto

logy

extract

extract

1:1

catalog

catalog

catalog

Value from clinical informatics

EMR – Patient Journey System

• Single integrated clinical record

• Covers all areas of specialist MH care – initial referral to full service discharge

• Total of 190,000 records with 35,000 active patients

• 5,000 unique users log-in per month

• 300,000 documents created per month

CRIS – EMR research tool

• Complete clinical data – structured, semi-structured and unstructured

• Extracted, pseudonymised and deidentified, including free text

• Searchable repository

• Pseudonym attached to samples

• Linked to imaging and biological datasets

-10

12

3

16 18 20 22 24

time(years)

MMSE score

Response to cholinesterase inhibitors

Four years of data

Real world patients

3500 patient years of treatment

treatment

Trust Electronic

Patient Record

ePJS

Research

Information System

CRIS

S

e

c

u

r

e

N

e

t

w

o

r

k

Data Interchange with

GP and other health

care systems

Personal

Health Record -

HealthVault

…including Patient Reported Outcome

Measures, trials information,

engagement ….

Mobile Device

Connection

Center

‘My SLaM’ Portal…..

Partner Devices

BioResource

Consent for

consent

Page 18

Page 19

Big data and pervasive computing;

hypothesis driven translational research

• There is a signature in blood, in CSF and in brain

• Adding complexity adds value but adds complexity!

• Sorting this out will require sample sets bigger than are likely to be

collected by single studies

• Sorting it out is worthwhile because

- It may reveal new therapeutic targets

- It almost certainly is essential for experimental medicine

• We need to collaborate, to re-utilise data, to innovate in study design, to

use multiple platforms, to solve the governance, security and

interoperability issues ….

….and have very big computers and smart people !

Biomarkers and mechanisms in AD

More info

EMIF general

Bart Vannieuwenhuyse (bvannieu@its.jnj.com)

Simon Lovestone (simon.lovestone@kcl.ac.uk)

Johan van der Lei (j.vanderlei@erasmusmc.nl)

EMIF-Platform

Johan van der Lei (j.vanderlei@erasmusmc.nl)

Patrick Genyn (pgenyn1@its.jnj.com)

EMIF-Metabolics

Ulf Smith (ulf.smith@medic.gu.se)

Dawn Waterworth (Dawn.M.Waterworth@gsk.com)

EMIF-AD Pieter Jelle Visser (pj.visser@maastrichtuniversity.nl)

Simon Lovestone (simon.lovestone@kcl.ac.uk)

Mike Krams (mkrams@its.jnj.com)

www.emif.eu (coming soon)