Elena Camporesi (Sweden)
Institute of Neuroscience and Physiology, University of Gothenburg
Department of Psychiatry and Neurochemistry
Pharmacist by training, Elena Camporesi recently completed her PhD studies in neuroscience at the University of Gothenburg, Department of Psychiatry and Neurochemistry (Sweden). Her PhD work focused on the study of different synaptic proteins as possible biomarkers in neurodegenerative disorders, mainly during Alzheimer’s disease. Being passionate about fluid biomarkers development, Elena is continuing her work on the neuroscience field, expanding her research on other protein, including tau protein, combining immunoassays and mass spectrometric methods.

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 Conference Calendar

QUANTIFICATION OF MULTIPLE TAU PHOSPHORYLATIONS AND ISOFORMS ACROSS DIFFERENT TAUOPATHIES IN HUMAN BRAIN USING HIGH-RESOLUTION MASS SPECTROMETRY

Session Name
1530 - TAU PROPAGATION AND CELLULAR INTERACTIONS 2 (ID 72)
Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 114
Lecture Time
10:25 AM - 10:40 AM
Presenter

Abstract

Aims

Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), Pick’s disease (PiD), and corticobasal degeneration (CBD) are neurodegenerative disorders characterized by the aggregation and spreading of tau protein. Due to similarities, it is currently problematic to chemically characterize the tau pathology in these diseases. Our aim was to develop a multiplex assay to quantify isoform-specific and phospho-tau species in brain and cerebrospinal fluid (CSF) of these diseases.

Methods

CSF, soluble (tris-buffered saline, TBS), and sarkosyl-insoluble (SI) brain extracts from the aforementioned tauopathies were immunoprecipitated using antibodies targeting all four tau regions. More than 50 tryptic peptides were monitored by liquid chromatography/high-resolution mass spectrometry, using isotope-labelled protein and peptide standards for quantification.

Results

In both brain fractions, all tau isoforms were detected, while only N-terminal peptides were observed in CSF. The 0N and 1N isoforms were most abundant in all samples. Preliminary data from the SI fraction of pooled brain extracts, 3R was more abundant in PiD, 4R in PSP and CBD, while in AD and controls they had similar abundance. Further, peptides from the microtubule-binding region were markedly more abundant in AD, indicating aggregation of these species. In the TBS fraction, immunoprecipitated with the HT7 antibody, phosphorylated tau was markedly increased in AD compared with the other groups; in particular doubly (p212+p217 and p231+p235) and triply (p231+p235+p238) phosphorylated peptides.

Conclusions

This novel assay can identify isoform differences across tauopathies. Measurement of multiply phosphorylated peptides could clearly differentiate AD from the other tauopathies. Additional data from the sample set is under way and will be presented.

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