Alzheimer's Plasma Extension (APEX)

August 14, 2026 updated by: Paul S. Aisen, University of Southern California

The goal of this observational study is to learn how Alzheimer's disease-related blood biomarkers, brain amyloid, and memory and thinking abilities change over time. The study will include up to 3,000 people who previously did not qualify for an anti-amyloid Alzheimer's disease prevention trial based on their amyloid eligibility. Participants may have previously screened for the AHEAD 3-45 Study, A4 Study, or another anti-amyloid Alzheimer's disease prevention trial.

The main questions this study aims to answer are:

  • Can Alzheimer's disease-related blood tests help predict future buildup of amyloid in the brain?
  • How are changes in Alzheimer's disease-related blood biomarkers related to changes in brain amyloid, memory, thinking, and self-reported cognitive function?
  • Do these changes differ based on factors such as sex, APOE genetic status, race, ethnicity, socioeconomic status, or social factors?

Participants will be followed for about 6 years. They will complete memory and thinking assessments and questionnaires and provide blood samples. Some participants may also be asked to take part in optional activities, including brain imaging with positron emission tomography (PET) or magnetic resonance imaging (MRI), digital cognitive assessments, and questionnaires about habits and social factors.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama, Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Alzheimer's Institute
      • Sun City, Arizona, United States, 85351
        • Banner Sun Health Research Institute
    • California
      • Irvine, California, United States, 92697
        • University of California, Irvine
      • Los Angeles, California, United States, 90033
        • University of Southern California
      • Palo Alto, California, United States, 94304
        • Stanford University
      • San Diego, California, United States, 92123
        • Sharp Neurocognitive Research Center
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
      • Walnut Creek, California, United States, 94598
        • University of California, Davis
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University
      • Washington D.C., District of Columbia, United States, 20060
        • Howard University
    • Florida
      • Delray Beach, Florida, United States, 33445
        • Brain Matters Research
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic, Jacksonville
      • Lady Lake, Florida, United States, 32159
        • K2 Medical Research - The Villages
      • Maitland, Florida, United States, 32751
        • K2 Medical Research, LLC
      • Miami, Florida, United States, 33135
        • Gonzalez MD & Aswad MD Health Services
      • Miami Beach, Florida, United States, 33140
        • Wien Center for Clinical Research
      • Orlando, Florida, United States, 32803
        • Charter Research
      • Tampa, Florida, United States, 33613
        • University of South Florida - Health Byrd Alzheimer Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Kansas
      • Fairway, Kansas, United States, 66205
        • University of Kansas
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • University of Kentucky
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Boston University
      • Boston, Massachusetts, United States, 21155
        • Brigham and Women's Hospital
      • Plymouth, Massachusetts, United States, 02360
        • Headlands Eastern MA LLC
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan, Ann Arbor
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic, Rochester
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Washington University, St. Louis
    • Nevada
      • Las Vegas, Nevada, United States, 89101
        • Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas
    • New York
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • Rochester, New York, United States, 14620
        • University of Rochester Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Lou Ruvo Center for Brain Health, Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Central States Research, LLC
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • UNIVERSITY of PENNSYLVANIA
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Butler Hospital Memory and Aging Program
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • Ralph H. Johnson VA Health Care System
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University Medical Center Center for Cognitive Medicine
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas, Southwestern MC at Dallas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • Houston Methodist Neurological Institute
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
    • Virginia
      • Norfolk, Virginia, United States, 23510
        • Eastern Virginia Medical School at Old Dominion University
      • Richmond, Virginia, United States, 23294
        • National Clinical Research Inc.
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington, Memory and Brain Wellness Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

This study will enroll up to 3,000 participants who previously screen failed from an anti-amyloid preclinical Alzheimer's disease (AD) trial based on amyloid eligibility. Up to 1,500 participants will have previously consented to the AHEAD 3-45 Study and screen failed due to a negative amyloid PET scan or prior to PET imaging. Up to 1,500 participants will have previously screen failed from the A4 Study or another anti-amyloid preclinical AD trial based on amyloid eligibility.

Description

Inclusion Criteria:

  1. Documentation of the participant's informed consent to study procedures and for the use of protected health information (HIPAA Authorization, or local, regional or country-specific equivalent). Informed consent processes and documentation must adhere to state laws/local requirements, including consent provided by the participant's legally authorized representative (LAR), responsible next of kin, surrogate consent with assent, etc.
  2. Previously consented to participate in an anti-amyloid preclinical AD study (e.g., AHEAD 3-45, A4 or other anti-amyloid preclinical AD study).
  3. Has screening results that did not meet amyloid eligibility criteria for an anti-amyloid preclinical AD trial (e.g., AHEAD 3-45, A4, or other anti-amyloid preclinical AD study).

  4. As assessed by the site PI, participant is likely to be able to comply with the protocol, including completion of all required procedures for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy in English or Spanish sufficient for compliance with required testing procedures.

    For participants who screen failed from the AHEAD 3-45 Study:

  5. Has AHEAD 3-45 screening plasma biomarker results required for determining eligibility to participate in the AHEAD 3-45 Study.

Exclusion Criteria:

  1. Current treatment with an FDA approved medication for Alzheimer's disease, including prior or current treatment with a prohibited medication.
  2. Enrollment in another investigational study, or intake of investigational drug, within 30 days prior to screening, or five half-lives of the investigational drug, whichever is longer, unless it can be documented that the participant was in the placebo treatment arm.

  3. Screen failed from an anti-amyloid preclinical AD trial (e.g. AHEAD 3-45, A4 or other anti-amyloid preclinical AD trial) due to not meeting basic inclusion criteria (i.e., age requirement; current diagnosis of AD dementia).

    For participants participating in the optional amyloid PET imaging sub-study:

  4. Is pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort 1: AHEAD 3-45 Participants
Approximately 1,500 participants who consented to participate in the AHEAD 3-45 Study and screen failed due to a negative amyloid PET scan or screen failed prior to PET imaging
Radiation: NAV4694
Amyloid PET imaging with NAV4694 injection
Other Names:
  • [18F]NAV4694
Cohort 2: Other Anti-Amyloid Prevention Trial Participants
Approximately 1,500 participants who previously screen failed from the A4 Study or another anti-amyloid prevention trial on the basis of amyloid eligibility.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of change from Baseline through Month 72 in plasma beta-amyloid (Aβ) 40 or 42 ratio
Time Frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72
Change in plasma Aβ42/Aβ40 ratio over the longitudinal follow-up period will be assessed using repeated blood-based biomarker measurements.
Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72
Rate of change from Baseline through Month 72 in plasma phosphorylated tau (ptau) 217
Time Frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72
Assess longitudinal changes from initial visit in plasma phosphorylated tau (ptau) 217 ratio using a proteomics assay
Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Change from Baseline through Month 72 as measured by the Preclinical Alzheimer Cognitive Composite 5 (PACC5)
Time Frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72
The Preclinical Alzheimer Cognitive Composite 5 (PACC5) is a composite measure of episodic memory, timed executive function, semantic memory, and global cognition. It includes: Free and Cued Selective Reminding Test (FCSRT), using the Free + Total Free and Cued Recall score (0-96, higher scores indicate better performance); delayed Paragraph Recall (0-25, higher scores indicate better recall); Digit Symbol Substitution Test (DSST), number correctly completed in 90 seconds (0-91, higher scores indicate better performance); Mini-Mental State Examination (MMSE) (0-30, higher scores indicate better performance); and Category Fluency, number of appropriate words generated, with higher scores indicating better performance.
Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72
Rate of Change from Baseline through Month 72 as measured Cognitive Function Index (CFI)
Time Frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72
The participant-reported Cognitive Function Index (CFI) assesses the participant's perceived ability to perform high-level functional tasks in daily life and overall cognitive functional ability. Only the participant-CFI portion will be administered. Participants rate their own abilities using 18 questions. The total participant-CFI score ranges from 0 (minimum) to 18 (maximum), with higher scores indicating greater impairment. The CFI may be self-administered or completed as an interview conducted by clinical site personnel in person or, if necessary, over the phone.
Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Amyloid Positron Emission Tomography (PET)
Time Frame: Initial amyloid PET to longitudinal amyloid PET, approximately 4 years (plus or minus 1 year)
Change in brain amyloid levels as measured by amyloid positron emission tomography (PET) imaging. Longitudinal amyloid PET will be compared with the participant's initial amyloid PET scan to assess change in brain amyloid over time.
Initial amyloid PET to longitudinal amyloid PET, approximately 4 years (plus or minus 1 year)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Collaborators

National Institute on Aging (NIA)
Alzheimer's Therapeutic Research Institute
Alzheimer's Association
Alzheimer's Clinical Trials Consortium (ACTC)

Investigators

  • Study Director: Paul Aisen, MD, University of Southern California (USC) Alzheimer's Therapeutic Research Institute (ATRI)
  • Study Director: Reisa Sperling, MD, Brigham and Women's Hospital and Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2023

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

February 21, 2023

First Submitted That Met QC Criteria

May 14, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

August 18, 2026

Last Update Submitted That Met QC Criteria

August 14, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATRI-013
  • 5R01AG054029 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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