Yuqi Cai
Pronouns
She/Her/Hers
Job Title
Technical Research Assistant
Academic Rank
Department
Neurology
Authors
Yuqi Cai, Lei Liu, MD, PhD, Jasmeer Chhatwal, MD, PhD and Dennis J Selkoe, MD
Principal Investigator
Dennis J Selkoe
Research Category: Neurosciences
Tags
Recently, plasma levels of phosphorylated tau protein are demonstrated as useful biomarkers for Alzheimer’s disease (AD) diagnosis. However, due to limited understanding of tau isoforms and their pathological relevance in diverse tauopathies, most tau biomarker identifications remain specific to one tau post-translational modifications and may not reflect the diversity in AD. To better understand tau pathological changes to monitor disease progress, we need to detect tau molecular abnormalities in the brain, cerebrospinal fluid (CSF), and plasma. This study is to establish next generation fluidic biomarkers targeting emerging tau abnormalities for AD prognosis and diagnosis. We have developed five p-Tau assays (pT175, pT181, pT217, pT231/S235, and pTPP) on the Millipore SMCxPRO platform and observed increased tau levels in AD brain extracts, compared to age-matched controls. CSF pT181 and pT217 levels strongly correlated with decreased amyloid-beta and increased total and phosphorylated tau levels. However, there was no correlation between plasma pT181/pT217 levels and PiB PET signals in the Harvard Aging Brain Study (HABS). We are now systematically examining the capture and detector antibodies to observe clinical relevance. Together, the novel p-Tau assays will deepen our understanding of tau protein in AD pathology.
Recently, plasma levels of phosphorylated tau protein are demonstrated as useful biomarkers for Alzheimer’s disease (AD) diagnosis. However, due to the substantial heterogeneity of tau isoforms and limited understanding of their pathobiological relevance in diverse tauopathies, most tau biomarker identifications remain specific to one tau post-translational modification, which would not reflect the diversity of tau species observed in AD. To better understand the tau pathological changes, it is important to detect tau molecular changes in the brain, cerebrospinal fluid (CSF) and plasma. This study aims to establish next generation fluidic biomarkers targeting emerging tau abnormalities for AD prognosis and diagnosis. We have developed five p-Tau assays (pT175, pT181, pT217, pT231/S235, and pTPP) on the Millipore SMCxPRO platform and observed increased levels of tau in neuropathologically confirmed AD brain tissue relative to control brains. CSF pT181 and pT217 levels strongly correlated with decreased amyloid-beta and increased total and phosphorylated tau levels. However, there was no correlation between plasma pT181/pT217 levels and PiB PET signals in the Harvard Aging Brain Study (HABS). We are now systematically examining the capture and detector antibodies to observe clinical relevance. Together, the novel p-Tau assays will deepen our understanding of tau protein in AD pathology.
