Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia and Frontotemporal Dementia (SLD3)

Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia and FTD

This study is designed to learn more about overall tau burden in the brain of patients with Primary Progressive Aphasia (PPA) and Frontotemporal Dementia.

Study Overview

• Status: Completed
• Conditions: Primary Progressive Aphasia; Behavioral Variant of Frontotemporal Dementia; Frontotemporal Dementia, Behavioral Variant
• Intervention / Treatment: Drug: F-18 AV 1451

Detailed Description

Primary progressive aphasia (PPA) is an umbrella term that encompasses a group of neurodegenerative syndromes characterized by varying combinations of progressive speech and language problems. Three clinical variants of PPA have been described and are well recognized: the agrammatic variant characterized by grammatical errors in speech and writing and typically associated with phonetic errors in speech; the semantic variant characterized by poor naming from loss of knowledge about the meaning of words; and the logopenic variant characterized by word retrieval problems and poor sentence repetition from impairment of working memory and phonemic errors. Pathological studies of PPA patients that died with postmortem examination of their brains have demonstrated that PPA is associated with a number of different abnormal cellular proteins that do not have perfect associations with the three PPA variants. One such protein is the microtubule associated protein, tau, which is the most common abnormal protein found in the brains of patients with PPA. Tau is an important protein that has been linked to the neurodegenerative process in many diseases. No neuroimaging studies have investigated tau deposition in PPA and hence the binding characteristics of AV-1451 (the Tau binding drug used in this study) in PPA are unknown. Understanding the binding characteristics of AV-1451 is crucial to help determine whether it can serve as a biomarker for tau deposition in the brains of patients with PPA.

FTD or Frontotemporal Dementias, including bvFTD, will also be included in this study.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be over the age of 18
• Must speak English as your primary language
• Must have an informant who can provide independent evaluation of functioning
• Must present with a chief complaint of progressive impairment of speech/language or changes in behavior
• Must fulfill diagnostic criteria for Primary Progressive Aphasia or Frontotemporal Dementia

Exclusion Criteria:

• Any subject who is mute or whose speech is unintelligible will be excluded
• All subjects with concurrent illnesses that could account for speech and language deficits, such as traumatic brain injury, strokes or developmental syndromes, and subjects meeting criteria for another neurodegenerative disease, such as amnestic Alzheimer's type dementia, dementia with Lewy bodies, progressive supranuclear palsy, and corticobasal syndrome will be excluded
• All pregnant, post-partum and breast-feeding women will be excluded
• Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, etc.), 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).
• Subjects who meet criteria for PPA and have mild behavioral changes, eye movement abnormalities or mild limb apraxia but who do not meet diagnostic criteria for, progressive supranuclear palsy or corticobasal syndrome respectively, will also be excluded.
• Subjects will be excluded from the study if they have any of the following genetic conditions which can increase the chance of cancer: Cowden disease, Lynch syndrome, hypogammaglobulinemia, Wiskott-Aldrich syndrome, and Down's syndrome.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tau PET Scan, F-18 AV 1451; All subjects will receive a Tau PET scan.	Drug: F-18 AV 1451; Tau binding agent
No Intervention: Normal Controls; Subjects from our NIH funded Mayo Clinic Study of Aging (U01 AG006786) who have completed the identical tau-PET protocol with AV-1451 and MRI and clinical protocols. These participants were not consented or enrolled in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of PPA Subjects That Showed Elevated Tau PET Binding Compared to Normal Controls	The percentage of subjects who showed elevated tau PET binding in the following five categories: PPA Clinical Variant-logopenic (lvPPA), PPA Clinical Variant-semantic (svPPA), PPA Clinical Variant-agrammatic (agPPA), no clinical variant-healthy, and Unclassified Variant (PPA-U).	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signature Patterns of Regional Tau PET Binding in Clinical PPA Variants	To determine whether each of the three clinical PPA variants (logopenic (lvPPA), semantic (svPPA) and agrammatic (agPPA)) has a signature pattern of regional tau PET binding by measuring the level of tau PET binding in each PPA variant. 0=represents no specific uptake pattern; 1=specific uptake pattern	1 Week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in Patterns of Tau PET Binding	To identify variability in patterns of tau PET binding using principal component (PC) analysis based on regional [18F]AV-1451 uptake to identify patterns between the three clinical variants: lvPPA, svPPA and agPPA independent of clinical diagnosis among PPA subjects. Two PCs were utilized to determine the number of participants who fell into the following 4 categories based on regional [18F]AV-1451 uptake patterns: low PC1/high PC2, low PC1/low PC2, high PC1/high PC2 and high PC1/low PC2. The first principal component (PC1) is a weighted sum of regional data where the weights are chosen so that PC1 has maximum variation across subjects. PC1 can be thought of as the "best" single-number summary of the regional data in a given modality. The second principal component (PC2) is a weighted sum of regional data with weight chosen so that (1) PC2 is completely uncorrelated with PC1 and (2) PC2 has maximum variation after accounting for PC1.	1 Week

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Keith A Josephs, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: April 7, 2016
• First Submitted That Met QC Criteria: April 7, 2016
• First Posted (Estimated): April 13, 2016

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 7, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: FTD; bvFTD; PPA
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Communication Disorders; Language Disorders; Aphasia; Speech Disorders; Frontotemporal Lobar Degeneration; Frontotemporal Dementia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: 16-001703; 1R21NS094684-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No