The Bateman lab investigates the causes and methods of diagnosis and treatment of Alzheimer’s disease (AD), utilizing a wide variety of assays and techniques from basic applications, such as quantitative measurement of stable-isotope labeled peptides to clinical translational studies of diagnostic and therapeutic biomarkers for AD.
Projects
Plasma Aßeta
Our lab has developed a highly sensitive and precise mass spectrometry-based blood test to detect Alzheimer’s disease amyloid plaques in individuals even before symptom onset. In this project, we aim to determine the relationship between blood amyloid-beta isoform levels, CSF amyloid-beta, and amyloid PET, using archived blood samples from cross-sectional and longitudinal studies of cognitively normal individuals, patients with Alzheimer’s disease, and other neurodegenerative dementias.
Additionally, we are conducting a cross-sectional clinical study involving 1,120 individuals (Study to Evaluate Amyloid in Blood and Imaging Related to Dementia: SEABIRD) recruited from clinics and communities. The goal is to assess the participant acceptability and validity of the blood Aβ test as a screening tool for brain amyloidosis.
ApoE
Apolipoprotein E (ApoE) is a 34 kDa glycoprotein essential for the transport and metabolism of lipids and cholesterol throughout the body. As the most significant genetic risk factor for the development of late-onset Alzheimer’s disease (AD), the APOE gene has been the focus of considerable biomedical research. The gene is polymorphic, with three high-frequency alleles. The ε2 allele is generally considered protective and is associated with a decreased risk of AD. In contrast, the ε4 allele is linked to an increased risk in a dose-dependent manner (~3-fold for heterozygotes and ~12-fold for homozygotes).
Despite nearly three decades of intense research, the complete mechanism by which the APOE alleles modulate AD risk and pathogenesis remains elusive. Current efforts in the Bateman lab on ApoE include the structural characterization of the various glycoforms of ApoE present in human blood, cerebrospinal fluid (CSF), and tissue lysates. In addition, we are assessing the value of adding peripheral ApoE measurements to our already high-performing blood-based Aβ test.
NfL
Neurofilament light-chain (NfL), a biomarker of neurodegeneration, is elevated in the cerebrospinal fluid (CSF) and blood of patients with Alzheimer’s disease (AD) and various other neurodegenerative diseases. However, NfL is poorly characterized at the protein structure and isoform level.
The overall goal of this project is to characterize NfL isoforms in human CSF and blood using immunoprecipitation-mass spectrometry (IP-MS). We aim to quantify total and phosphorylated NfL isoforms in AD and non-AD controls, and to compare concentrations and isoforms across multiple disease states.
Tau
Neurofibrillary tangles, another hallmark of Alzheimer’s disease (AD), are composed of phosphorylated and aggregated tau proteins. Unlike amyloid beta, which forms amyloid plaques outside cells, tau proteins are associated with stabilizing microtubules and are primarily found inside neurons. However, recent studies have shown that tau proteins can be secreted outside neurons under both physiological and pathological conditions in a regulated manner. Tau proteins have a longer half-life than amyloid beta and exist in multiple isoforms with various post-translational modifications (PTMs), including phosphorylation, which may further contribute to the disease.
The goal of the tau projects in our lab is to understand the metabolism of tau in the human central nervous system (CNS), which may serve as an accurate and early biomarker of AD and other tauopathies. We use quantitative and sensitive mass spectrometry methods to study the turnover and phosphorylation of tau in the brain, cerebrospinal fluid (CSF), and plasma.
SILQ
Our goal with stable isotope labeling and quantitative mass spectrometry imaging (SILQ) of Alzheimer’s disease pathology in the human brain is to measure, for the first time in human Alzheimer’s disease (AD) brain, the nanoscale structure and metabolism of neurons, tangles and amyloid plaques. We aim to understand how they are affected by AD and how this metabolism is related to cognition, function, and overall health.
Learn more at the WashU Medicine Tracy Family SILQ Center.