CONFORMATIONAL PROPERTIES OF MISFOLDED PROTEIN AGGREGATES IN CASES INVOLVING THE CO-OCCURRENCE OF PRION DIS…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG068359_075
- FAIN
- R00AG068359
- Recipient
- CASE WESTERN RESERVE UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $497,998
- Period
- Sep 1, 2022 – Aug 31, 2025
- Fiscal year
- 2022
- Place of performance state
- OH
- Source file
- FY2022_All_Assistance_Full_20261006.zip
Description
CONFORMATIONAL PROPERTIES OF MISFOLDED PROTEIN AGGREGATES IN CASES INVOLVING THE CO-OCCURRENCE OF PRION DISEASE AND ALZEHIMER'S DISEASE OR PRION DISEASE AND CTE - PROJECT SUMMARY/ABSTRACT THE CO-OCCURRENCE OF MORE THAN ONE PATHOGENIC PROTEIN IS A FREQUENT EVENT IN ACQUIRED AND IDIOPATHIC NEURODEGENERATIVE DISEASES. AMYLOID BETA (ASS) AND TAU PATHOLOGIES COEXIST IN ALZHEIMER'S DISEASE; A-SYNUCLEIN AND ASS IN PARKINSON'S DISEASE WITH DEMENTIA; TAR DNA-BINDING PROTEIN 43 AND TAU IN CORTICOBASAL DEGENERATION. RECENTLY, I STUDIED IATROGENIC CREUTZFELDT-JAKOB DISEASE (ICJD), A HUMAN PRION DISEASE ACQUIRED BY INFECTION, AND CHRONIC TRAUMATIC ENCEPHALOPATHY/POST-TRAUMATIC STRESS DISORDER (CTE/PTSD), A NEURODEGENERATIVE CONDITION SECONDARY TO REPETITIVE TRAUMA. A SUBSET OF ICJD FEATURED THE CO-OCCURRENCE OF PATHOGENIC OR DISEASE- RELATED PRION PROTEIN (PRPD) AND ASS, BOTH OF WHICH I SUGGESTED RESULT FROM HUMAN-TO-HUMAN TRANSMISSION. SIMILARLY, A SUBSET OF CTE/PTSD HARBORED PRPD AND PATHOGENIC TAU (TAUD). THE CO-EXISTENCE OF MULTIPLE PATHOGENIC PROTEINS IN NEURODEGENERATIVE CONDITIONS HAS NOT YET BEEN FULLY UNDERSTOOD. IN THIS K99/R00 I PROPOSE TO INVESTIGATE MOLECULAR CHARACTERISTICS OF CO-OCCURRING PROTEINOPATHIES IN ICJD, SPORADIC CJD (SCJD) AND CTE/PTSD AS WELL AS IN ANIMAL MODELS. IATROGENIC CJD AND CTE/PTSD OFFER THE UNIQUE ADVANTAGE TO STUDY THE MECHANISMS OF NON-AGE RELATED MULTIPROTEIN NEURODEGENERATION. THREE INTERRELATED SPECIFIC AIMS ARE PROPOSED. SPECIFIC AIM 1 FOCUSES ON CONFORMATIONAL PROPERTIES OF PRPD AND ASS AGGREGATES FROM CASES WITH ICJD AND SCJD ASSOCIATED WITH ASS PATHOLOGY COMPARED TO PRPD FEATURES IN ASS- NEGATIVE ICJD AND SCJD; LATE ONSET ALZHEIMER'S DISEASE WILL PROVIDE CONTROL DATA FROM CLASSIC ASS. SPECIFIC AIM 2 DEALS WITH CONFORMATIONAL FEATURES OF PRPD AND TAUD HARVESTED FROM CTE/PTSD CASES WITH BOTH PROTEINOPATHIES COMPARED TO CORRESPONDING CTE/PTSD CASES AFFECTED BY TAUD BUT NOT PRPD; CASES OF PRION DISEASE WILL SERVE AS CLASSIC PRPD CONTROLS.