Alzheimer’s Disease (AD) is the most common cause of dementia, and 6.2 million Americans are currently living with the disease. However, this number will reach 12.7 million by 2050. One major challenge in treating AD is that often patients are not diagnosed until significant damage to the brain is already present, prompting the need for novel biomarkers or measurable substances indicative of disease. New research from the Zhejiang University School of Medicine and the University of Washington School of Medicine identifies protein levels of NMDAR2A as a potential blood-derived biomarker for AD. 

First, the authors investigated extracellular vesicles that contain molecules secreted by cells. Extracellular vesicles are measured in the blood and carry proteins that mark them as brain derived. The scientists compared extracellular vesicles in a cohort of patients with Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and neurologically healthy controls. They found fewer vesicles that carried proteins called NMDAR2A in plasma from AD patients compared to PD and controls. NMDAR2A is involved in communication between neurons, and in AD this communication is disrupted, leading to loss of function and cell death. The authors validated this result in a second cohort of AD and healthy controls. Collectively, their findings suggest that neuron-derived extracellular vesicles may serve as a useful marker in distinguishing between AD and non-AD patients. 

Although the results of the present study are preliminary, the discovery of reduced NMDAR2A levels in extracellular vesicles derived from AD patients may lead to a novel biomarker of early AD progression. However, longitudinal studies are required to determine how extracellular vesicle levels of NMDAR2A change over disease progression and whether these levels can predict cognitive impairment. 

This study was led by Chen Tian, Dr. Jing Zhang, Dr. Tessandra Stewart, and Dr. Min Shi at the Zhejiang University School of Medicine and the University of Washington School of Medicine. 

Managing Correspondent: Alex Lish 

Original Journal Article: “Blood extracellular vesicles carrying synaptic function- and brain-related proteins as potential biomarkers for Alzheimer’s disease”, Alzheimer’s & Dementia 

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