Raw data proteomic study in genetic frontotemporal dementia (GENFI study)

We used an untargeted mass spectrometric approach, tandem mass tag (TMT) proteomics, for the identification of biomarker signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the GENetic FTD Initiative (GENFI) were analysed, including 107 presymptomatic (44 C9orf72, 38 GRN, 25 MAPT) and 55 symptomatic (27 C9orf72, 17 GRN, 11 MAPT) mutation carriers as well as 76 mutation-negative controls (‘non-carriers’). We found both shared and specific proteomic alterations in each genetic form of FTD. Among the proteins significantly altered in symptomatic mutation carriers compared to non-carriers, we found that YWHAZ, YWHAG, UCHL1, NPTXR, NPTX2 and FABP3 were changed across all three genetic forms, as well as in patients with Alzheimer’s disease from previously published datasets. We observed differential changes in lysosomal proteins among symptomatic mutation carriers with marked abundance decreases in MAPT carriers. Further, we identified mu..., Participants and sample collection
Participants were recruited from the GENFI study, which includes individuals with a diagnosis of FTD due to a pathogenic mutation in MAPT, GRN, or C9orf72 (symptomatic mutation carriers), at-risk first-degree relatives (presymptomatic mutation carriers), and non-carriers (mutation-negative first-degree relatives from the same families). Demographics of the cohort are described in Table 1.
Participants were assessed using a standardised history and examination and were classified as symptomatic if they met consensus diagnostic criteria (51, 52). The CDR Dementia Staging Instrument with National Alzheimer Coordinating Centre Frontotemporal Lobar Degeneration component (CDR® plus NACC FTLD) was used to assess disease severity, and the CDR® plus NACC FTLD sum of boxes (SOB) was used for quantitative analyses in this paper. Participants underwent Volumetric T1-weighted MRI scans. More details on clinical evaluation and imaging can be found in Supplementary ..., , # Raw data proteomic study in genetic frontotemporal dementia (GENFI study)

[https://doi.org/10.5061/dryad.r7sqv9snk](https://doi.org/10.5061/dryad.r7sqv9snk)

## Description of the data and file structure

The data corresponds to the normalised relative abundances of proteins in cerebrospinal samples of genetic frontotemporal dementia participants and controls. The data was obtain by Tandem Mass Tag LC-MS.

CSF was collected in polypropylene tubes through a lumbar puncture and centrifuged to remove insoluble material and cells. Supernatants were aliquoted and stored at -80 °C within 2 hours after collection. CSF samples (25 µL) were reduced by the addition of Tris(2)-carboxyethylphosphine (TCEP) in sodium deoxycholate (DOC), and triethylammonium bicarbonate (TEAB) to a final concentration of 5 mM TCEP (1% DOC, 100 mM TEAB). Following incubation at 55 °C for one hour, samples were equilibrated to room temperature (RT). Carbamidomethylation was performed by adding iodoacetamide to a con...