pet & mri imaging in alzheimer’s...
TRANSCRIPT
![Page 1: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/1.jpg)
PET & MRI Imaging in Alzheimer’s Disease
Bruce Crosson, PhD
Department of Neurology
Emory University
![Page 2: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/2.jpg)
Positron Emission Tomography (PET) Imaging: How Does It Work?
+ -
Annihilation
Detector
Detector
![Page 3: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/3.jpg)
PET Scanner
![Page 4: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/4.jpg)
Types of PET Scans for Alzheimer’s Disease
Amyloid PETFlorbetapir (Amyvid), Florbetaben (Neuraceq), Flutemetamol(Vizamyl)
Tau PET
Glucose Metabolism PET (Fluorodeoxyglucose, FDG)
![Page 5: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/5.jpg)
Why use PET for Alzheimer’s disease?
Recent research has shown that information provided by amyloid PET scans can lead to changes in medications and/or counseling that are consistent with PET scan findings (presence of absence of Alzheimer’s disease pathology).
![Page 6: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/6.jpg)
What is magnetic resonance imaging?
Magnetic resonance imaging uses a very high magnetic field and computer-generated radio waves to create images of the brain and other organ systems. The high magnetic field causes the protons in your body to align with the magnetic field, and the radio waves perturb the protons, causing them to give off weak signals that are used to make images of the brain or other organs.
![Page 7: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/7.jpg)
MRIScanner
![Page 8: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/8.jpg)
Some Kinds of Magnetic Resonance Imaging
Structural Magnetic Resonance Imaging
Magnetic Resonance Angiogram
Cerebral Blood Flow
Functional Magnetic Resonance Imaging
![Page 9: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/9.jpg)
MRI and Alzheimer’s Disease
Detection of atrophy associated with Alzheimer’s disease
Rule out structural changes associated with other brain conditions
![Page 10: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/10.jpg)
A proteomic approach to resolve racial differences in Alzheimer’s
disease biomarkers
Erica ModesteGraduate Student – Molecular and Systems Pharmacology
Emory Goizueta Alzheimer’s Disease Research Center
![Page 11: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/11.jpg)
• AD is a neurodegenerative disease characterized by progressive memory loss
• AD is a proteinopathy defined by two neuropathologies in the brain:
• Amyloid-beta (Aβ) plaques
• Tau tangles
• Currently no effective therapies (Prince et al, 2015 & Weuve
et al, 2014)
• Failure of current treatments has been attributed to initial treatment being administered at too advanced of a stage of
AD. (Salloway et al, 2014, Morris et al, 2011, & Sperling et al 2011)
Alzheimer’s disease
![Page 12: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/12.jpg)
Decreases in Aβ and elevations in tau in CSF have high specificity and sensitivity for distinguishing between healthy controls and AD (Henry et al, 2013 & Hansson, 2006) )
Cerebrospinal fluid can aid in the early detection of AD
Control AD0
200
400
600
800
Aβ
42
p < .0001
Control AD0
100
200
300
Tau
p < 0.0001
Aβ
42
(p
g/m
L)
Tau
(p
g/m
L)
![Page 13: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/13.jpg)
The impact of race on AD
• Biomarker research is predominantly conducted in Caucasian populations
• There is an increased incidence of AD in African Americans
• The diagnosis of AD in African Americans is often delayed and have reduced rates of enrollment in clinical trials
• African Americans have lower levels of tau compared to Caucasians in CSF (Howell et al., 2017, Morris et al., 2019)
• Aβ levels are similar between races
• Tau levels differ between races
Caucasian (Cau)
African American (AA)
Control AD0
200
400
600
800
Aβ
42
p < .0001p < 0.0001
Control AD0
100
200
300
Tau
p < 0.0001p < 0.0001
Cau AA Cau AA0
200
400
600
800
Aβ
42
p < 0.0001
p < 0.0001
Control AD
p < 0.0001
p < 0.0001
Cau AA Cau AA0
100
200
300
Tau
p = 0.003
p < 0.0001
Control AD
p < 0.0001
p = 0.003
Aβ
42
(p
g/m
L)
Aβ
42
(p
g/m
L)
Tau
(p
g/m
L)
Tau
(p
g/m
L)
![Page 14: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/14.jpg)
Proteins are the “working molecules” of the body
~25,000genes
~1,000,000Modified Proteins
~100,000transcripts
Central Dogma
![Page 15: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/15.jpg)
Proteins are the “working molecules” of the body
~1,000,000Modified Proteins
Skaper. Int Rev Neurobiol. 2012;102:277-316
![Page 16: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/16.jpg)
Discovery Proteomic Biomarker Study in AD CSF
Control ADMass Spectrometry
Quantification of:~3,000 proteins
Higginbotham et al., bioRxiv, 2019
![Page 17: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/17.jpg)
Resolving global differences in cerebrospinal fluid proteome using Correlation Network Analysis
Network Analysis is premised on the understanding that proteins respond to biological stimuli as a “system”, changing expression as groups or “modules”
M2
M1 M3
M6 M4
M5
Dendrogram
M = module
Pro
tein
Exp
ress
ion
S1 S2 S3 S4
Protein X
Pro
tein
Exp
ress
ion
S1 S2 S3 S4
Protein Y
M1
![Page 18: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/18.jpg)
Defining communities of proteins in CSF using WGCNA resulted in the formation of 21 modules
![Page 19: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/19.jpg)
The M2 module most strongly correlated to CSF tau levels
![Page 20: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/20.jpg)
Interestingly, this M2 module also exhibited racial specificity
![Page 21: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/21.jpg)
Interestingly, this M2 module also exhibited racial specificity
![Page 22: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/22.jpg)
The M2 module includes MAPT, which encodes tau
Top 100 proteins in M2 Blue module
![Page 23: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/23.jpg)
100 proteins in M2 Blue module
The M2 module was also enriched in proteins involved in biological processes known to be related to tau
![Page 24: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/24.jpg)
Conclusions & Future Directions
100 proteins in M2 Blue module
Conclusions
- Communities of proteins in the CSF differ by disease and race.
Provides insight into the underlying biology and pathways that differ by race which allows us to prioritize of race-specific
biomarkers
Future Directions
• Replicate this analysis in a larger, racially balanced cohort across brain and CSF
![Page 25: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/25.jpg)
Acknowledgements
Funding
PI: Dr. Nicholas Seyfried
Fellow Lab Members:
Dr. Eric Dammer
Dr. Duc Duong
Dr. Lingyan Ping
Dr. Measho Abreha
Dr. Erik Johnson
Dr. Lenora Higginbotham
Dr. Sruti Rayaprolu
Dr. Kathleen Carter
Pritha Bagchi
Luming Yin
Kiaiming Xu
Qi Guo
Sean Kundinger
Sally Zhang
Cheyenne Hurst
Sydney Sunna
Christine Bowen
Collaborators:
Dr. Allan Levey (Emory)
Dr. James Lah (Emory)
Grants from the Accelerating Medicine Partnership AD
(U01AG046161-02), the National Institute on Aging
(R21AG054206, 5R01AG053960, RF1AG057470, and
RF1AG057471), the NINDS Emory Neuroscience Core
(P30NS055077), NIA Diversity Supplement
(U01AG061357), and the Emory Alzheimer’s Disease
Research Center (P50AG025688).
25
Me: Erica Modeste
![Page 26: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/26.jpg)
THE IMPORTANCE OF BIOMARKERS
& MINORITY REPRESENTATION
John Dwyer
President, Global Alzheimer’s Platform Foundation
![Page 27: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/27.jpg)
Global Alzheimer’s Platform Foundation
Mission: The Global Alzheimer’s Platform (GAP) Foundation is a patient-centric, non-profit organization dedicated to speeding the delivery of innovative therapy to those in need by reducing the time and cost of Alzheimer’s disease (AD) clinical trials.
What We Do:
• GAP-Net site network: unique network of institution and private sites aligned to a single central IRB and set for rapid start-up
• Enable clinical trials:
• Site Selection and Accelerated Study Start-Up Services
• GAP Participant Services (GPS) and Recruitment Assistance
• Additional Services: site optimization, protocol implementation tools, etc.
• Innovative Initiatives in North America: Medicare Advantage Program, pre-screening tools/processes, Lyft transportation, Citizen Scientist Award, Alliance Communities, etc.
![Page 28: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/28.jpg)
Alzheimer’s Disease by the Numbers
• Hispanics/Latinos are about 1.5 times as likely to have Alzheimer’s as older Caucasians1
• African Americans are twice as likely to have Alzheimer’s in comparison to older Caucasians1
9/15/2020 Confidential and Proprietary Information 28
Alzheimer’s disease is the 6th leading cause of death in the United States1
More than 5 million Americans are living with Alzheimer’s,
and two-thirds of them are women
1 in 3 seniors dies with Alzheimer’s or another dementia.
It kills more than breast cancer and prostate cancer combined1
Older Blacks/African Americans and Hispanics/Latinos are disproportionately more likely to have Alzheimer’s or other dementias
1Alzheimer’s Association. Alzheimer’s Disease Facts and Figures. 2020.
![Page 29: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/29.jpg)
Importance of Early Detection in AD
9/15/2020 Confidential and Proprietary Information 29
Researchers believe future treatments will be most effective when administered early on in the disease stage.1
A cognitive assessment evaluates different areas of brain function like memory, processing speed, and language. 1
As a result, early detection of Alzheimer’s disease will be critical.
Getting a baseline assessment is important to set a benchmark of your brain health for a future comparison.
In addition to cognitive assessments, the recent development of biomarkers for Alzheimer’s enables even earlier detection of the disease.
A biomarker is a measurement of what is happening inside your body, typically shown by laboratory and/or imaging tests2
1Alzheimer’s Association. Alzheimer’s Disease Facts and Figures. 2020.2National Institute of Aging. Biomarkers for Dementia Detection and Research. June 2020.
![Page 30: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/30.jpg)
Biomarkers in Alzheimer’s Disease
• Biomarker tests will help physicians diagnose Alzheimer’s and identify which individuals should receive treatments when they are available. Biomarkers also will be critical for monitoring the effects of treatment.
Minority representation in clinical trials evaluating biomarkers is essential to ensure biomarkers and future Alzheimer’s therapies work in all races and ethnicities.
Drs. Howell & Garrett of Emory University have recently determined that race matters when looking at cerebrospinal fluid (CSF) – a leading biomarker in Alzheimer’s disease.
African Americans had lower levels of biomarkers p-tau and AB40, but still had signs of cognitive decline.
The studies concluded diagnosing AD in African Americans, especially early/prodromal AD, is especially challenging. These differences in biomarkers may lead to an under-diagnosis of Alzheimer’s. 1,2
• Researchers believe that biomarkers, in combination with a commonly-used and validated cognitive assessment such as the Mini-Mental State Examination (MMSE), will increase physician efficiency and improve accurate diagnoses of AD. 3
• The most effective biomarker test or combination of tests may differ depending on where the individual is on the disease continuum and other factors.
9/15/2020 Confidential and Proprietary Information 30
1Howell et al. Alzheimer's Research & Therapy. 2017; 9(88)2Garrett et al. JAMA Network Open. 2019; 2(12)
3 Mattke et al. Diagnosis Assessment & Disease Monitoring. 2020; 12:e12081
![Page 31: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/31.jpg)
What You Can Do Today
![Page 32: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/32.jpg)
THANK YOU!
John Dwyer, PresidentGlobal Alzheimer’s Platform Foundation
1101 K St, NW, Suite 400
Washington, DC 20005
www.globalalzplatform.org
![Page 33: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/33.jpg)
COGNITIVE EMPOWERMENT PROGRAM –PHYSICAL ACTIVITY LIVE SESSIONS
AYOTONI ARIYO, ACSM-CPT
RESEARCH EXERCISE
PHYSIOLOGIST
![Page 34: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/34.jpg)
PHYSICAL ACTIVITY SESSIONS
• Full body workout (Aerobic & Resistance training)
• Balance, Functional Fitness, Dual Tasking
• Modifications to exercises
• Exercise along with trainer
• 45 Minute session – all fitness levels welcome
![Page 35: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/35.jpg)
FUNCTIONAL FITNESS
Maintaining and Improving day-to-day quality of life
Simulate real-life/daily activities
![Page 36: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/36.jpg)
DUAL TASKING EXERCISE
• Working on memory and recall
• Quick math + Exercise Game
• Examples:
• Walking while counting backwards from 100 by threes (97, 94, 91…)
• Balance on one foot while recalling past meals you ate that day/week
• Many more exercises – get creative!
![Page 37: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/37.jpg)
YOU’RE INVITED
SESSION REGISTRATION: HTTP://BIT.LY/CEPLIVEREG
PHYSICAL ACTIVITY 10 – 10:45AM ON
WEDNESDAYS
ALSO OFFERED: YOGA, TAI CHI, COGNITIVE TRAINING
![Page 38: PET & MRI Imaging in Alzheimer’s Diseasealzheimers.emory.edu/documents/combined915.pdfAlzheimer’s disease is the 6th leading cause of death in the United States1 More than 5 million](https://reader033.vdocuments.us/reader033/viewer/2022051909/5ffd371cef0e314f973933ef/html5/thumbnails/38.jpg)
THANK YOU!