Biomarker Profiling in Individuals at Risk for Prion Disease

Inclusion Criteria: 1. 1\. Aged 18 - 85, 2. One of the following: 1. Known carrier of pathogenic PRNP mutation 2. History of probable or definite prion disease in biological parent and other family members 3. Non-carrier family members and/or unrelated previously enrolled negative control volunteers 3. Medically safe to undergo blood draw, lumbar puncture and cognitive testing, 4. Adequate visual and auditory acuity to complete cognitive testing, 5. Fluent in English, 6. At least 5 years of education, 7. Capable of providing informed consent and following study procedures, 8. No contraindications to MRI scanning as determined via the Martinos Center MRI Screening process (for PRNP mutation carriers ONLY) Exclusion Criteria: 1. Any CNS disease other than asymptomatic or early prion disease, such as clinical stroke, brain tumor, multiple sclerosis, significant head trauma with persistent neurological or neurocognitive deficits, Alzheimer's disease, Parkinson's disease, frontotemporal lobar degeneration or other known neurodegenerative disease, 2. History of alcohol or other substance abuse or dependence within the past two years, 3. Any significant systemic illness or unstable medical condition or pregnancy that could represent safety risk or affect participation in the study, 4. Coagulopathy or anti-coagulant therapy (such as Coumadin) increasing the risk for phlebotomy or lumbar puncture resulting in PT/PTT and INR within 1.5 standard deviation over the upper normal limit.