Brigham and Women's Hospital
Brigham and Women's Hospital
Neurally-derived exosomes for the diagnosis and staging of sporadic Alzheimer's disease
Alzheimer's disease (AD) research is entering the exciting phase in which the huge amount of research effort over the last 30 years is now being translated into test drugs. However, recent drug trials have highlighted a need for better diagnosis of study participants, and development of markers that can be used to monitor response to therapy. Two proteins are strongly linked to AD: the tau protein and the amyloid beta-protein (Abeta). Measurement of tau and Abeta in the fluid that bathes the brain (cerebrospinal fluid, or CSF) and sophisticated brain imaging, can be used to diagnose early symptomatic stages of AD. Such approaches are now being used in clinical trials, however, brain imaging is expensive and can only be done at specialized sites and CSF sampling is unpopular with patients and is rarely done more than once. Thus, there is an urgent need for less costly and intrusive tests. Ideally such a test could be performed using blood taken at a routine visit to a local doctor. But the contents of blood are influenced by many organs and therefore changes in blood might not be sensitive to minor changes in brain that occur early in AD. Recently it was discovered that brain cells release small packages, referred to as extracellular vesicles, which have contents similar to brain cells. These extracellular vesicles can pass from the brain into the blood and therefore provide a unique opportunity to detect changes occurring in the brain. Here we propose to isolate extracellular vesicles from blood and analyze their tau and Abeta levels. The ultimate goal of this work is to develop a blood test to diagnose individuals with early stage AD and to identify those at risk of developing this terrible disease.