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Scientific article
Open access
English

Plasma proteome profiling identifies changes associated to AD but not to FTD

Published inActa neuropathologica communications, vol. 10, no. 1, 148
Publication date2022-10-22
First online date2022-10-22
Abstract

Background: Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process.

Methods: Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis.

Results: Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified.

Conclusions: We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.

eng
Keywords
  • AD
  • Alzheimer’s disease
  • FTD
  • Frontotemporal dementia
  • Plasma biomarkers
  • Somascan
  • Humans
  • Female
  • Middle Aged
  • Aged
  • Male
  • Frontotemporal Dementia / diagnosis
  • Frontotemporal Dementia / genetics
  • Proteome
  • Proteomics
  • Frontotemporal Lobar Degeneration / diagnosis
  • Frontotemporal Lobar Degeneration / pathology
  • Pick Disease of the Brain
  • Biomarkers
Affiliation Not a UNIGE publication
Funding
  • ZonMw - [733050206]
Citation (ISO format)
MOFRAD, R Babapour et al. Plasma proteome profiling identifies changes associated to AD but not to FTD. In: Acta neuropathologica communications, 2022, vol. 10, n° 1, p. 148. doi: 10.1186/s40478-022-01458-w
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Article (Published version)
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Identifiers
ISSN of the journal2051-5960
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Technical informations

Creation12/16/2022 7:19:00 AM
First validation12/16/2022 7:19:00 AM
Update time03/16/2023 10:34:38 AM
Status update03/16/2023 10:34:36 AM
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