2023 Alzheimer's Association Research Fellowship (AARF)

Targeting Cervical Lymphatics to Identify Biomarkers for Early AD Detection

What changes in the lymphatic system are associated with preclinical Alzheimer’s?

Yijun Pan, Ph.D.
University of Melbourne
Parkville, Australia

Background

Alzheimer’s is a progressive disease, and because of this, scientists are looking for ways to detect and diagnose it at an early, “preclinical” stage, before memory loss and other cognitive (brain function) changes become evident. Traditional methods of diagnosing Alzheimer’s involve measurements of biomarkers (or biological markers) such as the levels of tau or beta-amyloid (changes in these proteins are hallmark brain changes in Alzheimer’s). These methods, however, often involve using positron imaging tomography (PET) brain scans or collecting samples of cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord). Such methods are expensive and invasive, and they may not detect disease at a sufficiently early stage.

The lymphatic system, which includes lymph nodes and lymphatic vessels, is a drainage system that the body uses to “flush out” unwanted substances. Recent studies suggest that the brain clears dementia-related molecules through the cervical lymphatic system. This system includes lymphatic vessels that drain immune cells and molecules such as beta-amyloid from the brain to a special kind of lymph node called deep cervical lymph nodes.

Research Plan

Dr. Yijun Pan and colleagues believe that levels of specific dementia-associated immune cells in the deep cervical lymph nodes may be useful as biomarkers of preclinical Alzheimer’s.  The researchers will use sophisticated biological and statistical methods to study the immune cells in the deep cervical lymph nodes of young genetically engineered Alzheimer’s-like mice (preclinical: before they develop symptoms). The team will identify the differences in immune cells found in the deep cervical lymph nodes of young genetically engineered Alzheimer’s-like mice and in cognitively unimpaired mice. Finally, Dr. Pan and colleagues will develop tests to detect Alzheimer’s-specific immune cells in the blood, lymph fluid, and CSF of both young (preclinical) and older (symptomatic) genetically engineered Alzheimer’s-like mice.

Impact

Results of this project may lead to new ways to diagnose Alzheimer’s early, before the onset of symptoms, when intervention is most helpful.