Molecular and Structural Imaging for Alzheimer's Disease

Overseen By Sarah M Boland, CCRP

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy

Disqualifiers: Stroke, Tumor, Poor vision, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand changes in the brains of individuals with Alzheimer's Disease over a year, using special brain scans to measure amyloid and tau proteins. The trial uses two types of PET scans to visualize these proteins: one with C-11 PiB (Pittsburgh Compound B) and the other with F-18 AV 1451 (Tauvid). Suitable candidates have ongoing Alzheimer's symptoms and a trusted person to provide information about their daily functioning. Participants must not have strokes or tumors that explain their symptoms, and they should not have severe vision problems or other conditions affecting brain imaging. As an unphased trial, this study offers a unique opportunity to contribute to the foundational understanding of Alzheimer's Disease.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you may be excluded if you are on medications that affect brain structure or metabolism, like chemotherapy.

What prior data suggests that these imaging techniques are safe for patients with Alzheimer's Disease?

Research has shown that F-18 AV 1451, also known as Tauvid, is generally safe for brain scans. The FDA has approved it for imaging tau, a protein linked to memory issues. Most side effects are mild, such as reactions at the injection site or minor symptoms in the body, while serious allergic reactions are rare.

Studies have found that C-11 PiB is commonly used in research to image amyloid, another brain protein associated with Alzheimer's. It provides a safe level of radiation for brain scans.

Both treatments are well-tolerated, with the most common issues being minor and temporary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses advanced imaging techniques to better understand Alzheimer's disease. Unlike current treatments that focus on managing symptoms, this study employs the C-11 PiB and F-18 AV 1451 PET scans to visualize amyloid plaques and tau tangles in the brain, which are hallmarks of Alzheimer's. These scans offer a non-invasive way to potentially diagnose and monitor the disease much earlier and more accurately. This could lead to earlier intervention and more targeted treatment options in the future.

What evidence suggests that this trial's imaging techniques could be effective for Alzheimer's Disease?

Research has shown that F-18 AV 1451, also known as Flortaucipir, effectively captures images of tau proteins in the brain. The FDA approved it because it helps identify tau build-up, a key indicator of Alzheimer's disease. This understanding can enhance knowledge of disease progression. In this trial, participants will undergo Tau PET scans using F-18 AV 1451.

Similarly, C-11 PiB is a PET scan tool that detects amyloid plaques in the brain. Studies indicate it can assist in diagnosing Alzheimer's by revealing amyloid build-up, which often occurs before symptoms appear. Participants in this trial will also undergo PiB PET scans using C-11 PiB. Both imaging methods offer valuable insights into brain changes linked to Alzheimer's, potentially aiding in early detection and monitoring. ^{6 7 8 9 10}

Who Is on the Research Team?

Jennifer Whitwell, Ph.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This study is for adults over 21 with Atypical Alzheimer's Disease, specifically those diagnosed with Logopenic Aphasia or Posterior Cortical Atrophy. Participants must have a person to report on their functioning and speak English as their primary language. They can't join if they've had strokes, tumors, severe memory issues early on, other neurodegenerative diseases, very poor vision, are pregnant/breastfeeding, or have MRI contraindications.

Inclusion Criteria

I have trouble finding the right words and forming sentences.

I have Alzheimer's with worsening memory loss or specific symptoms like LPA or PCA.

English is primary language

Exclusion Criteria

Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism (e.g. chemotherapy)

I do not have any other neurodegenerative disorders like frontotemporal dementia.

I have had a stroke or tumor that might be causing my symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo two Tau PET scans and two PiB PET scans to assess amyloid and tau burden

12 months

Follow-up

Participants are monitored for changes in amyloid and tau burden over a one year period

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• C-11 PiB
• F-18 AV 1451

Trial Overview The trial is using advanced brain imaging techniques (F-18 AV 1451 and C-11 PiB) to investigate the presence of amyloid and tau proteins in patients' brains. It aims to see how these protein levels change over one year in individuals with atypical forms of Alzheimer's disease.

How Is the Trial Designed?

Group I: Tau PET Scan, F-18 AV 1451 Experimental Treatment 2 Interventions

All subjects will receive two Tau PET scans during this study.

Group II: PiB PET Scan, C-11 PiB Experimental Treatment 2 Interventions

All subjects will receive two PiB PET scans during this study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

The use of [18F]PM-PBB3 tau PET imaging successfully identified tau deposition in a patient with frontotemporal dementia (FTD) caused by a MAPT mutation, indicating its potential as a diagnostic tool for this condition.

In a comparison of tau PET tracers, [18F]PM-PBB3 showed positive retention in all patients with both 3-repeat and 4-repeat tau, while AV-1451 was less consistent, highlighting [18F]PM-PBB3's broader utility in detecting tau strains associated with FTD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation. Su, Y., Fu, J., Yu, J., et al.[2021]

In a study involving 30 participants (11 with semantic dementia, 9 with Alzheimer's disease, and 10 healthy controls), only a minority of early-onset semantic dementia patients showed amyloid-β deposition, while late-onset semantic dementia patients were PIB-negative, suggesting a lack of Aβ accumulation in this group.

The findings indicate that amyloid-β deposition is not associated with late-onset semantic dementia, and while some early-onset patients may exhibit Aβ deposition, they do not present the typical memory or visuospatial deficits seen in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid deposition in semantic dementia: a positron emission tomography study. Brown, EE., Graff-Guerrero, A., Houle, S., et al.[2021]

The FDA-approved radiotracer 18F-flortaucipir is increasingly used in PET imaging to visualize tau pathology in patients with cognitive impairment, particularly Alzheimer's disease.

An international consensus has been established to standardize the procedural use of 18F-flortaucipir PET imaging, which will enhance its application in clinical practice for diagnosing and managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. Tian, M., Civelek, AC., Carrio, I., et al.[2022]

This study found a strong correlation (Pearson r = 0.81) between flortaucipir PET imaging results and levels of abnormally phosphorylated tau (Ptau) in brain tissue from patients with dementia, suggesting that flortaucipir can effectively reflect tau pathology in Alzheimer's disease.

The research indicates that while flortaucipir PET correlates well with Ptau levels, it does not show a significant relationship with amyloid-β (Aβ1-42), highlighting its potential specificity for tau-related changes in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. Pontecorvo, MJ., Keene, CD., Beach, TG., et al.[2021]

In a study involving 17 Alzheimer's disease (AD) patients and 11 healthy controls, PET imaging with the tracer [(11)C]PIB showed significantly increased uptake in several brain regions, indicating higher amyloid accumulation in AD patients.

The most notable increases in [(11)C]PIB uptake were found in the frontal cortex (163% of control mean) and posterior cingulate (146%), aligning with known patterns of amyloid pathology in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Kemppainen, NM., Aalto, S., Wilson, IA., et al.[2020]

The first fully automated synthesis of the radiotracer [11C]PIB for imaging amyloid plaques in Alzheimer's disease was successfully developed, allowing for efficient production in clinical settings.

This automated process yields [11C]PIB with a high radiochemical purity of over 99% and a specific activity of 20-60 GBq/micromol, enabling timely preparation for PET scans within 25 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer. Verdurand, M., Bort, G., Tadino, V., et al.[2020]

18F-Florbetapir PET imaging is effective for detecting β-amyloid plaques, while 18F-Flortaucipir PET is useful for visualizing tau protein tangles, both of which are critical for diagnosing Alzheimer's disease (AD).

Combining data from both amyloid and tau PET scans can enhance the accuracy of differential diagnosis and prognosis in patients with mild cognitive impairment or suspected AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series. James, OG., Linares, AR., Hellegers, C., et al.[2023]

The review highlights that various tau PET tracers, including the FDA-approved 18F-flortaucipir, effectively discriminate between Alzheimer's disease (AD) patients and healthy controls, with effect sizes (Cohen's d) typically ranging from two to three in affected brain regions.

While second-generation tau tracers show improved off-target binding profiles, they do not significantly enhance sensitivity for distinguishing AD from healthy controls, suggesting a potential limit in the affinity of current tracers for tau fibrils.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Sensitivity of Tau Tracers for the Discrimination of Alzheimer's Disease Patients and Healthy Controls by PET. Mohammadi, Z., Alizadeh, H., Marton, J., et al.[2023]

A strong correlation was found between the retention ratios of (11)C-Pittsburgh compound B (PiB) and (18)F-florbetapir in the same individuals, indicating that both radioligands effectively measure amyloid-β levels in the brain, with a Spearman correlation coefficient ranging from 0.86 to 0.95.

The study established reliable cutoff thresholds for determining amyloid-β positivity or negativity that can be interconverted between PiB and florbetapir, enhancing the consistency of diagnostic criteria across different imaging methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. Landau, SM., Breault, C., Joshi, AD., et al.[2022]

In a study involving 28 patients with mild-to-moderate Alzheimer's disease, treatment with bapineuzumab significantly reduced cortical fibrillar amyloid-beta load as measured by (11)C-PiB PET scans over 78 weeks, showing a mean difference of -0.24 compared to placebo.

While most adverse events were mild to moderate, two patients experienced transient cerebral vasogenic edema, indicating that while bapineuzumab is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Rinne, JO., Brooks, DJ., Rossor, MN., et al.[2021]

The [18F]flortaucipir PET imaging technique has demonstrated high affinity for tau proteins associated with Alzheimer's disease and shows excellent accuracy in distinguishing AD from other conditions, indicating strong analytical and clinical validity.

While phases 1 and 2 of the maturity assessment for [18F]flortaucipir PET have been largely achieved, further research is needed to fully establish its clinical utility, particularly in early detection and healthcare outcomes for patients with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase biomarker development framework. Wolters, EE., Dodich, A., Boccardi, M., et al.[2021]

Flortaucipir PET imaging shows a strong correlation with tau burden in Alzheimer's disease (AD), indicating its effectiveness in evaluating tau levels in AD patients, although there are exceptions where the uptake does not match due to other conditions.

In contrast, flortaucipir has limited effectiveness in assessing tau burden in non-Alzheimer's tauopathies, suggesting a need for improved imaging techniques to better detect tau in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of regional tau distribution by Tau-PET and Post-mortem neuropathology in a representative set of Alzheimer's & frontotemporal lobar degeneration patients. Gatto, RG., Carlos, AF., Reichard, RR., et al.[2023]

Citations

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Longitudinal Amyloid Imaging Using 11C-PiB: Methodologic ... At baseline, mean R1 values of 11C-PiB were 0.87 ± 0.05 in patients with AD, 0.89 ± 0.03 in MCI patients, and 0.87 ± 0.04 in controls. At follow ...

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Pittsburgh Compound B Imaging & Progression Prediction Preclinical AD as detected by PET PiB is not benign, as it is associated with progression to symptomatic AD.

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7. jnm.snmjournals.org jnm.snmjournals.org/content/48/1/128

Biodistribution and Radiation Dosimetry of the Amyloid ... Conclusion: The established clinical dose of 11C-PIB required for 3-dimensional PET amyloid imaging has an acceptable effective radiation dose. This dose is ...

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Pittsburgh Compound B - an overview The 11C-labeled Pittsburgh compound B (PIB) has been the most extensively used radiotracer for research Aβ PET imaging. ... C-PIB was the first amyloid ...

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11 C-PiB PET assessment of change in fibrillar amyloid-β ... Carbon-11-labelled Pittsburgh compound B (11C-PiB) PET is a marker of cortical fibrillar amyloid-β load in vivo. We used 11C-PiB PET to investigate whether ...