| Title: |
Detection of TDP-43 seeds in CSF of presymptomatic and symptomatic genetic FTD/ALS |
| Authors: |
Dellarole, Ilaria Linda; Aprea, Vittoria; Catania, Marcella; Battipaglia, Claudia; Romeo, Aurora; Villa, Cristina; Burato, Anna; Celauro, Luigi; Bella, Eleonora Dalla; Riva, Nilo; Salvi, Erika; Rossi, Giacomina; Fede, Giuseppe Di; Legname, Giuseppe; De Houwer, Julie F H; Alberici, Antonella; Borroni, Barbara; Seelaar, Harro; van Swieten, John C; Moda, Fabio; Caroppo, Paola |
| Contributors: |
I.L. Dellarole; V. Aprea; M. Catania; C. Battipaglia; A. Romeo; C. Villa; A. Burato; L. Celauro; E.D. Bella; N. Riva; E. Salvi; G. Rossi; G.D. Fede; G. Legname; J.F.H. De Houwer; A. Alberici; B. Borroni; H. Seelaar; J.C. Van Swieten; F. Moda; P. Caroppo |
| Publisher Information: |
Wiley Blackwell Publishing |
| Publication Year: |
2025 |
| Collection: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| Subject Terms: |
CSF; SAA; TDP‐43; amyotrophic lateral sclerosi; frontotemporal dementia; seed amplification assay; Settore BIOS-09/A - Biochimica clinica e biologia molecolare clinica; Settore BIOS-07/A - Biochimica; Settore MEDS-12/A - Neurologia |
| Description: |
Introduction: Seed amplification assays (SAAs) have shown promising results in detecting misfolded transactive response (TAR) DNA-binding protein 43 (TDP-43) in cerebrospinal fluid (CSF) of genetic frontotemporal dementia (FTD). To date, the use of SAA has yet to be evaluated in presymptomatic individuals. Methods: Thirty patients carrying GRN or C9orf72 mutations, 2 microtubule-associated protein tau (MAPT) carriers, 14 presymptomatic subjects, and 27 controls underwent CSF collection. We used SAA for detecting misfolded TDP-43 (TDP-43_SAA) and single molecule array (SIMOA) technology for neurofilament light chain (NfL) dosage. Results: TDP-43 seeding activity was detected in 67% of TDP-43-linked symptomatic patients, with a specificity of 93%. Almost half of presymptomatic subjects tested positive, mostly GRN carriers. Interestingly, among TDP-43_SAA positive presymptomatic individuals, two GRN carriers underwent phenoconversion. Discussion: TDP-43_SAA can also detect misfolded TDP-43 in the CSF of presymptomatic individuals. A possible link exists between positive TDP-43_SAA and conversion to the symptomatic phase. Highlights: Seed amplification assay of transactive response (TAR) DNA-binding protein 43 (TDP-43_SAA) can detect misfolded TDP-43 in the cerebrospinal fluid (CSF) of patients with genetic frontotemporal dementia (FTD), linked to GRN and C9orf72 mutations. TDP-43_SAA can detect misfolded TDP-43 also in the CSF of presymptomatic individuals. In both groups, most TDP-43_SAA positive cases were carriers of GRN mutation. Two GRN carriers that resulted TDP-43_SAA positive converted to the symptomatic phase of the disease. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41399249; info:eu-repo/semantics/altIdentifier/wos/WOS:001639607800001; volume:21; issue:12; firstpage:1; lastpage:9; numberofpages:9; journal:ALZHEIMER'S & DEMENTIA; https://hdl.handle.net/2434/1210599 |
| DOI: |
10.1002/alz.70989 |
| Availability: |
https://hdl.handle.net/2434/1210599; https://doi.org/10.1002/alz.70989 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.D577129A |
| Database: |
BASE |