Imaging Inflammation in Alzheimer's Disease

Imaging Inflammation in Elders With Different Clinical and Biomarker Profiles of Alzheimer's Disease

This study is being done to learn about inflammation and amyloid in Alzheimer's disease. A type of brain scan called a PET scan is used measure 1) inflammation and 2) abnormal accumulation of a the amount of a certain protein fragment called beta-amyloid (plaques) in the brain. These are thought to be involved in Alzheimer's disease. The investigators will also perform brain MRI and do tests to measure the participants' memory and thinking.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: 11C-PBR28; Drug: 18F-Florbetaben; Procedure: Lumbar puncture (optional)

Detailed Description

This study is being done to determine the relationship between inflammation, cognitive impairment, and amyloid burden in elderly subjects with different clinical and biomarker profiles of Alzheimer's disease (AD). Participants will undergo amyloid PET imaging with 18F-Florbetaben with target number of completers being 15 amyloid-positive elders with impairment, 15 amyloid-positive elders with normal cognition, 15 amyloid-negative elders with impairment, and 15 amyloid-negative elders with normal cognition. Subjects will undergo screen that includes neuropsychological testing, brain MRI, and PET imaging with 18F-florbetaben to define the above 4 groups. Subjects will have 11C-PBR28 PET imaging to measure the 18 kDa translocator protein (a marker of inflammation). Subjects will have the option to have lumbar puncture performed to measure CSF concentrations of amyloid,tau, phospho-tau, and inflammatory markers.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 60 and older.
2. Meet criteria for either a) amnestic mild cognitive impairment (single or mixed domain) or mild Alzheimer's disease, or b) have no cognitive impairment based on history, exam, neuropsychological testing, and consensus diagnosis. MCI and mild AD patients must have Clinical Dementia Rating scale score of 0.5 or 1. Unimpaired subjects must have Clinical Dementia Rating scale score of 0.
3. Subjects unable to provide informed consent must have a surrogate decision maker
4. Written and oral fluency in English or Spanish.
5. Able to participate in all scheduled evaluations and to complete all required tests and procedures.
6. In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.

Exclusion Criteria:

1. Past or present history of certain brain disorders other than MCI or AD.
2. Certain significant medical conditions, which make study procedures of the current study unsafe.
3. Contraindication to MRI scanning.
4. Conditions precluding entry into the scanners (e.g., morbid obesity, claustrophobia, etc.).
5. Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
6. Low affinity binding on TSPO genetic screen.
7. Participation in the last year in a clinical trial for a disease modifying drug for AD.
8. Inability to have a catheter in subject's vein for the injection of radioligand.
9. Inability to have blood drawn from subject's veins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amyloid-positive with cognitive impairment (AD); Amyloid-positive patients who already have cognitive impairment at the time of enrollment.	Drug: 11C-PBR28; 11C-PBR28 is a PET radioligand that binds to the 18 kDa translocator protein (TSPO), a marker of inflammation. 11C-PBR28 has previously been administered in humans. 11C-PBR28 will be administered at activity of up to 20 mCi per injection.; Other Names: 11C-[O-methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; Drug: 18F-Florbetaben; 18F-Florbetaben (Neuraceq) has FDA approval for human use in evaluation of Alzheimer's disease. 18F-Florbetaben will be administered at activity up to 8.1 mCi per injection.; Other Names: Neuraceq; Procedure: Lumbar puncture (optional); Subjects have the option to have lumbar puncture performed for the measurement of inflammatory markers in cerebrospinal fluid.; Other Names: LP
Active Comparator: Amyloid-positive without impairment (preclinical AD); Cognitively normal subjects who are amyloid-positive	Drug: 11C-PBR28; 11C-PBR28 is a PET radioligand that binds to the 18 kDa translocator protein (TSPO), a marker of inflammation. 11C-PBR28 has previously been administered in humans. 11C-PBR28 will be administered at activity of up to 20 mCi per injection.; Other Names: 11C-[O-methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; Drug: 18F-Florbetaben; 18F-Florbetaben (Neuraceq) has FDA approval for human use in evaluation of Alzheimer's disease. 18F-Florbetaben will be administered at activity up to 8.1 mCi per injection.; Other Names: Neuraceq; Procedure: Lumbar puncture (optional); Subjects have the option to have lumbar puncture performed for the measurement of inflammatory markers in cerebrospinal fluid.; Other Names: LP
Active Comparator: Amyloid-negative with cognitive impairment; Participants with cognitive impairment due to suspected non-AD pathophysiology	Drug: 11C-PBR28; 11C-PBR28 is a PET radioligand that binds to the 18 kDa translocator protein (TSPO), a marker of inflammation. 11C-PBR28 has previously been administered in humans. 11C-PBR28 will be administered at activity of up to 20 mCi per injection.; Other Names: 11C-[O-methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; Drug: 18F-Florbetaben; 18F-Florbetaben (Neuraceq) has FDA approval for human use in evaluation of Alzheimer's disease. 18F-Florbetaben will be administered at activity up to 8.1 mCi per injection.; Other Names: Neuraceq; Procedure: Lumbar puncture (optional); Subjects have the option to have lumbar puncture performed for the measurement of inflammatory markers in cerebrospinal fluid.; Other Names: LP
Active Comparator: Amyloid-negative without impairment (normal aging); Cognitively normal subjects who are amyloid-negative on PET, and lack signs of neurodegeneration from other biomarkers	Drug: 11C-PBR28; 11C-PBR28 is a PET radioligand that binds to the 18 kDa translocator protein (TSPO), a marker of inflammation. 11C-PBR28 has previously been administered in humans. 11C-PBR28 will be administered at activity of up to 20 mCi per injection.; Other Names: 11C-[O-methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; Drug: 18F-Florbetaben; 18F-Florbetaben (Neuraceq) has FDA approval for human use in evaluation of Alzheimer's disease. 18F-Florbetaben will be administered at activity up to 8.1 mCi per injection.; Other Names: Neuraceq; Procedure: Lumbar puncture (optional); Subjects have the option to have lumbar puncture performed for the measurement of inflammatory markers in cerebrospinal fluid.; Other Names: LP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
11C-PBR28 Binding	In vivo quantification radioligand binding to TSPO expression on microglia in the brain, reported as standardized uptake value ratio (SUVR).	Up to 1 year from screening

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-Florbetaben Binding	In vivo quantification of radioligand binding to Amyloid-Beta protein in the brain, reported as standardized uptake value ratio (SUVR).	Up to 1 year from screening
Cerebral Spinal Fluid (CSF) Biomarkers	Protein analysis of cerebral spinal fluid.	Up to 1 year from screening

Collaborators and Investigators

• Sponsor: Patrick Lao
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Patrick J Lao, Columbia University

Publications and helpful links

General Publications

• Klein J, Yan X, Johnson A, Tomljanovic Z, Zou J, Polly K, Honig LS, Brickman AM, Stern Y, Devanand DP, Lee S, Kreisl WC. Olfactory Impairment Is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease. J Alzheimers Dis. 2021;80(3):1051-1065. doi: 10.3233/JAD-201149.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: July 10, 2016
• First Submitted That Met QC Criteria: July 10, 2016
• First Posted (Estimated): July 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: aging; inflammation; mild cognitive impairment
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Inflammation
• Other Study ID Numbers: AAAO1151; 1K23AG052633-01 (U.S. NIH Grant/Contract)