Stable Isotope Labeling and Quantitative Mass Spectrometry Imaging of Alzheimer’s Disease Pathology in Human Brain

2017 and 2019

Our goal is to measure, for the first time in human Alzheimer’s disease brain, the metabolism of neurons (brain cells) and how they are affected by AD, and if this is directly related to tau accumulation inside the neuron affecting function and overall health. Further, we will measure plaque pathology and tau tangle growth. We have developed an advanced imaging protocol called SILK-SIMS, which enables us to image and measure neuron metabolism and plaque growth at the nanometer level; this allows us to see structures much smaller than cells and quantify changes during life and the disease process.

Neuronal metabolism and plaque growth is measured with a label given to patients (like a dye that tags newly made plaques and tangles), which we then image with SILK-SIMS, noting both the location and amount of neuronal metabolism or hypo-metabolism and plaque toxicity. We aim to measure neuronal metabolism (a proxy for function), tangle growth and plaque toxicity, using SILK-SIMS imaging, in the brains of people with mild to severe AD, and compare these measurements with those taken from patients without dementia. These findings will enable us to model how fast AD pathology occurs in the living human brain. This research is unique in that we will be providing the first direct measures of growth of AD pathology in the human AD brain by utilizing cutting-edge methodologies never before leveraged in the AD field. The outcomes will provide new insights in order to better understand tau and amyloid pathology, which can accelerate drug development and inform clinical trials. In addition, we will establish a blueprint for the investigation of other devastating such neurodegenerative diseases as Parkinson’s disease, frontal-temporal dementia and amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease).


Funding to Date

$300,000

Focus

Identification and Early Detection

Researchers

Randall J. Bateman, M.D.