Finding molecular signatures of Alzheimer’s disease in blood extracellular vesicles

2015

Challenge

No blood tests currently exist that can detect brain disorders like Alzheimer’s disease (AD) at an early stage or monitor the effectiveness of therapeutic interventions.

Advance

IRP researchers led by Dimitrios Kapogiannis, M.D., found that extracellular vesicles, believed to be released from nerve cells, can be isolated from blood samples. The team found that subjects with mild cognitive impairment and AD exhibit major abnormalities in the amounts of several proteins within extracellular vesicles; these proteins were already known to be involved in brain dysfunction and AD. Preliminary studies suggest that these abnormalities may be present up to 10 years before patients are formally diagnosed with the disease.

Impact

The findings, if confirmed in larger studies currently underway, suggest that neuron-derived extracellular vesicles circulating in the blood can identify individuals who will develop AD before the onset of symptoms.

Publications

Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, Abner EL, Petersen RC, Federoff HJ, Miller BL, Goetzl EJ. (2014). Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case – control study. Alzheimer's & dementia: the journal of the Alzheimer's Association. 11(6), 600-7.

Kapogiannis D, Boxer A, Schwartz JB, Abner EL, Biragyn A, Masharani U, Frassetto L, Petersen RC, Miller BL, Goetzl EJ. (2015). Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease. FASEB J. 29(2), 589-96.

Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Biragyn A, Masharani U, Frassetto L, Petersen RC, Miller BL, Kapogiannis D. (2015). Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer’s disease. Neurology. 85(1), 40-7.