Alzheimer’s disease is a devastating and progressive neurodegenerative disease affecting approximately 5.3 million people in the United States, including almost half of the population at 85 years and older. Microscopic hallmarks of the disease include neuritic plaques containing amyloid beta peptide and neurofibrillary tangles composed of tau. It is generally believed that Alzheimer’s-related changes begin in the brain at least a decade before the emergence of telltale symptoms. Now, a study from researchers at Rowan University develops a blood test which leverages the body’s immune response to detect an early stage of Alzheimer’s disease, referred to as the mild cognitive impairment (MCI) stage, with unparalleled accuracy in humans. The team state that in their study, involving 236 subjects, the test demonstrated an overall accuracy, sensitivity and specificity rate of 100% in identifying subjects whose MCI was actually caused by an early stage of Alzheimer’s disease. The opensource study is published in the journal Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.
Previous studies show that in cerebrospinal fluid (CSF), the most established biomarkers include Aβ42, total tau, and phosphorylated tau. A key limitation to the use of CSF is that it is obtained through a lumbar spinal puncture, which is considered invasive and not without risk. Parallel advancements for early Alzheimer’s disease detection have been made in neuroimaging, such as MRI and PET using tracers. However, the high cost of these procedures and inconsistencies in interpretation prohibits their use as initial disease screeners, and they may not be readily available to individuals in disadvantaged areas or remote locations. By contrast, procurement of blood is less invasive, and plasma proteins, lipids as well as proteins and microRNAs have all shown promise as biomarkers for early detection of Alzheimer’s disease pathology. The current study develops a blood test using autoantibody biomarkers which can accurately detect Alzheimer’s at an early point in the course of the disease when treatments are more likely to be beneficial, that is, before too much brain devastation has occurred.
The current study analyzed blood samples from 236 subjects, including 50 MCI subjects with low levels of amyloid-beta peptide in their cerebrospinal fluid. Employing human protein microarrays, each containing 9,486 unique human proteins that are used as bait to attract blood-borne autoantibodies, the lab identified the top 50 autoantibody biomarkers capable of detecting ongoing early-stage Alzheimer’s pathology in patients with MCI.
Results show that in multiple tests, the 50 biomarkers were 100% accurate in distinguishing patients with MCI due to Alzheimer’s from healthy age- and gender-matched controls. Data findings show that the selected MCI biomarker panel demonstrated similar high overall accuracy rates in differentiating patients with early Alzheimer’s at the MCI stage from those with more advanced, mild-moderate Alzheimer’s (98.7%), early-stage Parkinson’s disease (98.0%), multiple sclerosis (100%) and breast cancer (100%).
The group note that the utility of their MCI biomarker panel as a blood test for early detection of Alzheimer’s disease will hinge on a larger study using an independent patient cohort. However, they also point out that, because this blood-based diagnostic strategy is dependent on the presence of Alzheimer’s pathology which can be underway many years before symptoms emerge, their approach could open the door to even earlier pre-symptomatic detection of Alzheimer’s disease.
The team surmise their results show that it is possible to use a small number of blood-borne autoantibodies to accurately diagnose early-stage Alzheimer’s disease. For the future, the researchers state that their findings could eventually lead to the development of a simple, inexpensive and relatively non-invasive way to diagnose this devastating disease in its earliest stages.
Source: Rowan University
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