Autoimmune Features of Neurodegenerative Disorders

Neurodegenerative diseases are characterized by the misprocessing of specific proteins, but how and if this results in cell death is unknown. This study is being conducted to better understand the role of inflammation in Parkinson's disease (PD) and Alzheimer's disease (AD). Both AD and PD have long been known to feature prominent neuroinflammatory components. Preliminary studies have found autoimmune features in several patients including recognition of self-antigens by specific T cells. This study will test the hypothesis that AD and PD are associated with self-derived antigens (alpha-syn and tau protein) that become recognized by T cells during aging and disease. The overall aim is to identify antigenic responses associated with PD and AD. The specific aims include:

• Identify the protein(s) or protein segments that may trigger inflammation
• Identify the T cells (immune cells) that may recognize and kill brain cells (neurons and astrocytes)
• Identify the genetic profile associated with this immune response (genetic analysis of the immune system)

PD and age matched controls:

For PD participants (n=30):

Inclusion criteria

• Clinical diagnosed PD based on UK Brain Bank criteria for the clinical diagnosis of PD. And must demonstrate two of the following three, as modified from BioFIND criteria: rest tremor, rigidity, or bradykinesia, with dopaminergic medication benefit
• Age at recruitment ≥ 55
• Age at motor onset > 45
• PD onset age between 50-75 years
• Willingness to have genotyping and genetic studies

Exclusion criteria

• Atypical features indicative of a Parkinson-Plus disorder (Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD)) including cerebellar signs, supranuclear gaze palsy, apraxia and other cortical signs, or prominent autonomic failure, neuroleptic treatment at time of onset of parkinsonism, active treatment with a neuroleptic at time of study entry, history of repeated strokes with stepwise progression of parkinsonism, history of repeated head injury, history of definite encephalitis, prominent gait imbalance early in the course (< 5 years)
• History of Dementia
• Recent history of cancer (past 3 years), except skin cancer
• Autoimmune disease
• Disease of the immune system (e.g. chronic leukemia, HIV)
• On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
• Inability to provide informed consent.

For age-matched control participants (n=30):

Inclusion criteria

• Ages ≥55 years old
• With lack of PD in first-degree blood relatives
• Montreal Cognitive Assessment (MoCA): ≥26
• Willingness to have genotyping and genetic studies

Exclusion criteria

• Recent history of cancer (past 3 years), except skin cancer
• Autoimmune disease
• Disease of the immune system (e.g. chronic leukemia, HIV)
• On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
• Inability to provide informed consent

AD/aMCI and age matched controls:

For AD/aMCI participants (n=30):

Inclusion criteria

• Clinically diagnosed mild AD/amnestic MCI. The severity will be accessed through the Clinical Dementia Rating Scale (CDR). CDR equal to 0.5 or 1 will be necessary to meet criteria. Participants with advanced AD stage will not be capable to give their consent.
• Age ≥55 years old
• Mini-Mental State Exam (MMSE): 20-26
• Willingness to have genotyping and genetic studies

Exclusion criteria

• Other forms of dementia including frontotemporal dementia or other dementia associated with parkinsonism such as Dementia with Lewy bodies (DLB), or Parkinson's disease Dementia (PDD), Progressive Supranuclear Palsy or corticobasal degeneration.
• History of Parkinson's disease (PD)
• Recent history of cancer (past 3 years), except skin cancer
• Autoimmune disease
• Disease of the immune system (e.g. chronic leukemia, HIV)
• On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
• Inability to provide informed consent

For age-matched control participants (n=30):

Inclusion criteria

• Healthy volunteers ≥55 years old
• CDR: 0
• MoCA: ≥26
• Willingness to have genotyping and genetic studies

Exclusion criteria

• History of Parkinson's disease (PD)
• Recent history of cancer (past 3 years), except skin cancer
• Autoimmune disease
• Disease of the immune system (e.g. chronic leukemia, HIV)
• On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
• Inability to provide informed consent