PET Measures of CSF Clearance in Preclinical Alzheimer's Disease
Condition: Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Observational

Summary: 
      The purpose of this study is to measure cerebrospinal fluid (CSF) clearance. CSF cushions the
      brain from impact and carries waste products from the brain to the bloodstream. This process
      is known as clearance. Researchers have considered that impaired clearance of amyloid (a
      protein) from the aging brain causes buildup of amyloid in the brain and plays a role in
      increased risk for Alzheimer's disease. However, until recently, there has not been a method
      to measure CSF clearance. This study will examine CSF clearance using positron emission
      tomography (PET) scanning, which creates images of structures in the body and their
      functioning. This study will also measure the amount of two proteins, tau and amyloid, in the
      brain. Tau and amyloid are proteins that build up in the brains of people with Alzheimer's
      disease. An investigational compound (tracer) called [18F]MK-6240 is injected into the blood
      prior to the scan in order to take images of the CSF clearance and measure tau protein in the
      brain. This tracer is considered investigational because it is not approved by the US Food
      and Drug Administration (FDA) for clinical use and is only being used for research purposes.
    

Detailed description: 
      The impaired clearance of amyloid-β (Aβ) leading to the accumulation of Aβ plaques and
      consequent neurodegeneration, is a partially understood mechanistic hypothesis for late onset
      Alzheimer's disease (AD). Using Positron Emission Tomography (PET) and a tracer for tau
      lesions, with a low molecular weight that rapidly enters and clears the brain, the
      investigators developed, replicated, and validated a non-invasive method to estimate the
      clearance of CSF at ventricular and brain levels. The investigators propose to complete over
      five years, a 2y longitudinal study designed to test in preclinical AD the hypothesis that
      reduced CSF clearance measured with the tau tracer [18F]-MK6240 is predictive of: a) future
      amyloid lesions (PiB-PET or Florbetaben-PET); b) brain atrophy (MRI); and c) cognitive
      decline.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study will involve male and female volunteer subjects from any racial or ethnic group
        with a diagnosis normal cognition or mild cognitive impairment. The proposed sample is not
        intended to be representative of a general population, but it will approximate the samples
        recruited in NIH and industry sponsored FDA approved clinical trials targeting secondary AD
        prevention. At this stage of knowledge of human brain CSF clearance, a population based
        approach was considered premature and over cap funding to support a larger study was not
        permitted for RFA AG-17-055. Rather, our design uses Aβ enrichment to enable an efficient
        test of the CSF clearance hypothesis in a clinically relevant group.
      
Biospecimen description: 
      Blood incl. geneting testing/APE Genotyping, CSF