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Utilization of CerebroSpinal Fluid biomarkers for accurate identification of Alzheimer’s Disease

Background

Alzheimer’s disease (AD) is the sixth-leading cause of death in the United States. It represents a major health challenge due to the following:

1. Population aging is associated with increased prevalence of dementia, with increased awareness of AD as a cause of dementia.
2. AD is characterized by multiple other features besides dementia including confusion, language disturbances, and personality and behavioral changes with judgment impairment. These changes cause affected individuals to become more dependent and to also require specialized medical care, posing a heavier burden on the health care system.
3. The etiology of AD is still poorly understood; therefore, the available treatment options are limited to controlling AD in early stages only. Advanced AD stages still lack effective therapies.

Early diagnosis of AD is essential for treatment as well as to prevent its progression to a terminal disease. An accurate early diagnosis is critical, but because the clinical features of AD can overlap with multiple disorders that are common among elder patients, current clinical diagnosis of AD is unreliable, especially for AD in early-stages.

Technology Overview

In this invention, Boston Children’s Hospital researchers conducted a large-scale meta-analysis on individuals with AD and controls from 6 independent studies, in addition to an in-house study to validate the results. Three specific proteins were found to be highly accurate in assessing the brain pathology in Alzheimer’s Disease. The illustration below shows the main steps followed in identifying the biomarkers, and their high accuracy (sensitivity and specificity) represented by high AUROC values.

Applications

• Early diagnosis of Alzheimer’s Disease in individuals with clinical indications of high risk for the disease.
• Differentiating AD from other causes of dementia in individuals with vague overlapping clinical features of dementia.
• Assessing the brain pathology in affected individuals, including monitoring the response to therapy.

Advantages

• The ability to initiate treatment in early stages for patients who were diagnosed before developing advanced stages of AD. Early treatment can slow, prevent, or even reverse the progression of AD into advanced stages, leading to improved quality of life, more individual independence, and significant reduction in required healthcare.
• Identifying the response to therapy through monitoring brain pathology changes flowing a specific treatment.
• In connection with the previous point, further analysis of the treatment-response-relationship can provide insights into selecting the best treatment for an individual based on their biomarker profile.