# Autoimmune features of neurodegenerative disorders

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $804,632

## Abstract

Abstract:
Neurodegenerative diseases are characterized by the misprocessing of specific proteins, but how and if this
results in cell death has been unknown. This proposal supports collaborative research between immunology
and neuroscience laboratories with disease experts to pursue new findings that require such cross-disciplinary
collaboration. Our joint Preliminary Results provide the first direct evidence that Parkinson's disease (PD),
which has long been known to feature prominent neuroinflammatory components, is for at least many patients
in part an autoimmune disorder that features antigen presentation and specific T cell responses. The results
demonstrate that PD shares fundamental features with classical autoimmune disorders including Type-1
diabetes, multiple sclerosis, and rheumatoid arthritis. Our overall hypothesis is that PD is associated with self-
derived neoantigens that becomes increasingly expressed in aging or disease conditions. Our overall aim is to
identify the antigenic responses associated with PD and Alzheimer's disease (AD). We will identify 
α-synuclein-derived and tau-derived neoantigens in these patients and compare these profiles in patients with
PD, AD, age-matched controls and young controls. We will 1) identify epitopes that act as neoantigens in PD
and AD; 2) characterize the responsive T cells; 3) characterize the role of antigen presentation and T cell-
mediated neuronal death by animal models that express an HLA allele implicated in PD with high affinity to an
α-syn epitope. If the autoimmune features are confirmed, therapies used to treat other autoimmune disorders
such as tolerization can be used to treat PD.

## Key facts

- **NIH application ID:** 10214704
- **Project number:** 5R01NS095435-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Alessandro Sette
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $804,632
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214704

## Citation

> US National Institutes of Health, RePORTER application 10214704, Autoimmune features of neurodegenerative disorders (5R01NS095435-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214704. Licensed CC0.

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