This repository study at the University of Pennsylvania establishes a comprehensive biobank and longitudinal data repository for neurodegenerative disorders, collecting clinical data, biospecimens, and neuroimaging from patients with Alzheimer's disease, Parkinson's disease, PSP, FTD, ALS, CBS, and related conditions. The repository supports mechanistic research, biomarker discovery, and therapeutic development by providing well-characterized patient cohorts and standardized data collection protocols[1].
| Parameter | Value |
|---|---|
| NCT Number | NCT04715399 |
| Status | Recruiting |
| Study Type | Observational/Biobank |
| Conditions | PSP, PD, AD, FTD, ALS, CBS, CBD, MSA, PPA |
| Sites | University of Pennsylvania |
| Sponsor | University of Pennsylvania |
Neurodegenerative diseases represent a significant and growing health burden, affecting millions of individuals worldwide. The development of effective therapies requires a deep understanding of disease mechanisms, reliable biomarkers for diagnosis and progression tracking, and well-characterized patient cohorts for clinical trials[2]. Biobanks play a critical role in enabling this research by:
Standardized Sample Collection: Biobanks establish standardized protocols for collecting, processing, and storing biospecimens, ensuring quality and comparability across studies.
Longitudinal Data: Repeated assessments over time enable understanding of disease progression and identification of prognostic biomarkers[3].
Multi-Modal Integration: Combining clinical data, neuroimaging, genetics, and fluid biomarkers provides a comprehensive picture of disease[4].
Research Reproducibility: Well-annotated samples enable replication studies and validation of findings across independent cohorts.
The University of Pennsylvania has been a leader in neurodegenerative disease research for decades, with major contributions to:
Tau Biology: Understanding tau protein metabolism, phosphorylation, and aggregation mechanisms in PSP, CBD, and AD[1:1]
Biomarker Development: Pioneering fluid biomarker development including amyloid and tau in CSF, and neuroimaging biomarkers[3:1]
Genetics: Characterizing genotype-phenotype relationships in FTLD, MAPT mutations, GRN, and C9orf72 expansions[5]
Clinical Trials: Running landmark trials in AD, PD, PSP, and FTD[6]
Establish a Well-Characterized Cohort: Create a repository of patients with confirmed or suspected neurodegenerative disorders with detailed phenotypic characterization
Longitudinal Clinical Data Collection: Document disease progression through standardized clinical assessments at regular intervals
Build a Biospecimen Repository: Collect and bank DNA, plasma, serum, CSF, and tissue samples for future research
Support Mechanistic Research: Enable studies on disease mechanisms through access to patient samples and data
Accelerate Therapeutic Development: Facilitate clinical trial design and patient recruitment through well-characterized cohorts[6:1]
Core Assessment Battery:
Disease-Specific Scales:
| Disease | Primary Scale |
|---|---|
| PSP | PSP Rating Scale (PSPRS) |
| PD | MDS-UPDRS |
| AD | ADAS-Cog, MMSE |
| FTD | Frontotemporal Behavioral Rating Scale |
| CBS | CBD Rating Scale |
| MSA | UMSARS |
Cognitive Testing:
Functional Measures:
Behavioral Assessment:
Magnetic Resonance Imaging (MRI):
Positron Emission Tomography (PET):
Advanced Imaging:
Targeted Sequencing:
Genome-Wide Approaches:
Assessment Schedule:
Data Collection Points:
| Sample Type | Volume | Processing | Storage |
|---|---|---|---|
| DNA (blood) | 10 ml EDTA | Extracted and quantified | -20°C |
| Plasma | 10 ml EDTA | Centrifugation, aliquot | -80°C |
| Serum | 10 ml SST | Centrifugation, aliquot | -80°C |
| CSF | 10-20 ml | Centrifugation, aliquot | -80°C |
| Skin fibroblast | 3mm biopsy | Culture expansion | Liquid N2 |
| Brain tissue | Autopsy | Dissection, flash freeze | -80°C |
The repository supports analysis of multiple biomarker classes[4:1]:
Fluid Biomarkers:
Genetic Biomarkers:
The repository enables research into disease mechanisms:
Protein Aggregation Studies:
Cellular Models:
Gene Expression:
The well-characterized samples support biomarker research:
Discovery Cohorts: Large numbers of patients with detailed phenotypes enable identification of candidate biomarkers
Validation Studies: Longitudinal samples allow validation of progression markers
Multi-Modal Integration: Combining fluid, imaging, and genetic biomarkers provides comprehensive profiling[3:2]
The repository is essential for clinical trials[6:2]:
Patient Recruitment: Well-characterized cohorts enable efficient recruitment
Natural History: Progression data informs trial design and endpoint selection
Biomarker Qualification: Repository samples enable biomarker development for trial enrichment and endpoint selection
Target Validation: Patient samples support mechanistic studies of therapeutic targets
The repository supports biomarker-driven diagnosis:
Longitudinal data enables:
The repository enables:
Diagnosis: Confirmed or suspected diagnosis of:
Age: Any age (pediatric cases may be excluded for certain protocols)
Ability to Provide Informed Consent: Patient or legally authorized representative
Willingness to Donate Samples: Agreement to blood sampling and optional lumbar puncture
Penn's neurodegenerative repository has contributed to numerous major discoveries:
Tau Biology Advances: Understanding of tau phosphorylation, aggregation, and spread mechanisms[1:2]
Biomarker Development: Validation of CSF and imaging biomarkers for diagnosis and progression[3:3]
Genotype-Phenotype Relationships: Characterization of MAPT, GRN, and C9orf72 mutations[5:1]
Clinical Trial Design: Natural history data informing clinical trial endpoints[6:4]
The repository supports:
Frontotemporal dementia and related disorders: from molecules to therapeutics. Brain. 2020. ↩︎ ↩︎ ↩︎
Biomarkers of Alzheimer disease and other dementias. Neurology. 2010. ↩︎
Neuroimaging biomarkers for neurodegenerative disorders. Molecular Psychiatry. 2018. ↩︎ ↩︎ ↩︎ ↩︎
Fluid biomarkers in neurodegenerative disease. Current Opinion in Neurology. 2018. ↩︎ ↩︎
Clinical features of frontotemporal dementia. Journal of Neurology, Neurosurgery & Psychiatry. 2011. ↩︎ ↩︎
Clinical trials in frontotemporal dementia and related disorders. Alzheimer's & Dementia. 2023. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Neurofilament light chain as a biomarker in neurodegenerative disorders. Journal of Neurology. 2022. ↩︎