# Risk and Resilience, Clinical presentation, and Biomarker Profiles of Chronic Traumatic Encephalopathy and Related Dementias: The DIAGNOSE CTE Research Project II

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $3,289,394

## Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease diagnosed postmortem in people
exposed to repetitive head impacts (RHI) from football and other contact sports. NINDS consensus research
diagnostic criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES), were
published in 2021. However, we cannot diagnose CTE in life due to the following knowledge gaps: 1) TES criteria
do not include biomarkers, limiting disease specificity; (2) longitudinal studies are lacking; (3) biomarkers and
clinical features that distinguish CTE from other AD/ADRDs are unknown; and (4) risk/resilience factors of TES
are unclear, particularly social determinants of health (SDOH). In 2015, we were awarded a NINDS funded 7-
year U01 known as the DIAGNOSE CTE Research Project (DIAGNOSE), designed in part to develop biomarkers
of CTE. It enrolled 180 former football players (120 professional, 60 college) and 60 non-RHI controls, all males
ages 45-74. Baseline clinical exams, MRI, tau (flortaucipir) and amyloid PET, and blood draws were completed
in 2020. Four-year remote follow-ups, including in-home blood draws, were finished in Nov. 2023. We had a 90%
retention rate. The goals of this R01 are to retain and grown DIAGNOSE and examine the clinical and biomarker
course and profiles of TES (Aim 1); investigate risk/resilience factors of TES (Aim 2); and compare biomarkers
of amyloid (Aβ), p-tau, neurodegeneration, neuroinflammation, and white matter injury between TES and AD
syndromes (Aims 3-4). Our hypotheses are that TES has unique clinical and biomarker profiles, and RHI and
non-RHI risk factors influence the development of TES. There will be 3 groups: (1) Retention, 150 former football
players and 50 controls retained from DIAGNOSE; (2) Expansion, we will grow DIAGNOSE by newly recruiting
75 former college and professional football players and 25 controls; (3) AD, 50 Aβ+ participants with cognitive
impairment. In total, we will study 225 former football players, 75 controls, and 50 AD. Groups will be similar in
age (50+), sex (males), and race (40% Black). Participants will complete a single visit, including clinical exams,
SDOH measures, MRI, blood draw, and tau PET, at 1 of 5 P30 AD Research Centers: BU, UCSF, Arizona,
1Florida, or South Texas. Retention Cohort will have flortaucipir PET to study its longitudinal value. Expansion
Cohort will have MK-6240 PET to build on our R21. A subset of Retention (n=20) will have flortaucipir and MK-
6240 for tracer comparison. Blood will be analyzed for 6 p-tau epitopes, Aβ40/42, neuroinflammation, and white
matter injury. Retention Cohort will have legacy data for longitudinal study of outcomes (2-3 timepoints over 6-8
years). Expansion will contribute to pooled cross-sectional analyses. DIAGNOSE participants were asked for
brain donation; 8 have donated. This R01 will permit continued brain donation and clinical-pathological validation
studies. This R01 will retain and grow a u...

## Key facts

- **NIH application ID:** 10985074
- **Project number:** 1R01NS139383-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Michael Alosco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,289,394
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985074

## Citation

> US National Institutes of Health, RePORTER application 10985074, Risk and Resilience, Clinical presentation, and Biomarker Profiles of Chronic Traumatic Encephalopathy and Related Dementias: The DIAGNOSE CTE Research Project II (1R01NS139383-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10985074. Licensed CC0.

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