Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study
Abstract Introduction The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimic...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | Neurological Research and Practice |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42466-025-00417-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849225771214700544 |
|---|---|
| author | Laura Tzeplaeff Ana Galhoz Clara Meijs Lucas Caldi Gomes Andrej Kovac Amrei Menzel Hatice Değirmenci Abir Alaamel Hüseyin Can Kaya Ali Günalp Çelik Sine Dinçer Meltem Korucuk Sibel Berker Karaüzüm Elif Bayraktar Vildan Çiftçi Uğur Bilge Filiz Koç Antonia F. Demleitner Anne Buchberger Ricarda von Heynitz Vincent Gmeiner Christina Knellwolf Mohammed Mouzouri Joanne Wuu A. Nazli Başak Peter Munch Andersen Florian Kohlmayer Nicholas J. Ashton Wojciech Kuban Christof Lenz Mary-Louise Rogers Norbert Zilka Philippe Corcia Yossef Lerner Markus Weber Monika Turcanova Koprusakova Hilmi Uysal Michael Benatar Michael P. Menden Paul Lingor |
| author_facet | Laura Tzeplaeff Ana Galhoz Clara Meijs Lucas Caldi Gomes Andrej Kovac Amrei Menzel Hatice Değirmenci Abir Alaamel Hüseyin Can Kaya Ali Günalp Çelik Sine Dinçer Meltem Korucuk Sibel Berker Karaüzüm Elif Bayraktar Vildan Çiftçi Uğur Bilge Filiz Koç Antonia F. Demleitner Anne Buchberger Ricarda von Heynitz Vincent Gmeiner Christina Knellwolf Mohammed Mouzouri Joanne Wuu A. Nazli Başak Peter Munch Andersen Florian Kohlmayer Nicholas J. Ashton Wojciech Kuban Christof Lenz Mary-Louise Rogers Norbert Zilka Philippe Corcia Yossef Lerner Markus Weber Monika Turcanova Koprusakova Hilmi Uysal Michael Benatar Michael P. Menden Paul Lingor |
| author_sort | Laura Tzeplaeff |
| collection | DOAJ |
| description | Abstract Introduction The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need. Methods A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a presymptomatic and early ALS signature. Perspective The premodiALS study aim to identify a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early diagnosis and future clinical practice for ALS disease. |
| format | Article |
| id | doaj-art-73a2ead2607e4b24b3ef582086bf41bc |
| institution | Kabale University |
| issn | 2524-3489 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Neurological Research and Practice |
| spelling | doaj-art-73a2ead2607e4b24b3ef582086bf41bc2025-08-24T12:02:26ZengBMCNeurological Research and Practice2524-34892025-08-01711910.1186/s42466-025-00417-9Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS studyLaura Tzeplaeff0Ana Galhoz1Clara Meijs2Lucas Caldi Gomes3Andrej Kovac4Amrei Menzel5Hatice Değirmenci6Abir Alaamel7Hüseyin Can Kaya8Ali Günalp Çelik9Sine Dinçer10Meltem Korucuk11Sibel Berker Karaüzüm12Elif Bayraktar13Vildan Çiftçi14Uğur Bilge15Filiz Koç16Antonia F. Demleitner17Anne Buchberger18Ricarda von Heynitz19Vincent Gmeiner20Christina Knellwolf21Mohammed Mouzouri22Joanne Wuu23A. Nazli Başak24Peter Munch Andersen25Florian Kohlmayer26Nicholas J. Ashton27Wojciech Kuban28Christof Lenz29Mary-Louise Rogers30Norbert Zilka31Philippe Corcia32Yossef Lerner33Markus Weber34Monika Turcanova Koprusakova35Hilmi Uysal36Michael Benatar37Michael P. Menden38Paul Lingor39Department of Neurology, Rechts Der Isar Hospital of the Technical University MunichDepartment of Computational Health, Helmholtz MunichDepartment of Computational Health, Helmholtz MunichDepartment of Neurology, Rechts Der Isar Hospital of the Technical University MunichInstitute of Neuroimmunology, Slovak Academy of SciencesBitcare GmbH, Technical University of MunichDepartment of Neurology, Akdeniz University HospitalDepartment of Neurology, Akdeniz University HospitalDepartment of Neurology, Akdeniz University HospitalDepartment of Neurology, Akdeniz University HospitalDepartment of Neurology, Akdeniz University HospitalNeuromuscular Center, Antalya Education and Research HospitalDepartment of Neurology, Akdeniz University HospitalSchool of Medicine, Neurodegeneration Research Laboratory NDAL, Koç University, Research Center for Translational Medicine KUTTAMSchool of Medicine, Neurodegeneration Research Laboratory NDAL, Koç University, Research Center for Translational Medicine KUTTAMDepartment of Neurology, Akdeniz University HospitalNeurology Department, Çukurova UniversityDepartment of Neurology, Rechts Der Isar Hospital of the Technical University MunichDepartment of Neurology, Rechts Der Isar Hospital of the Technical University MunichDepartment of Neurology, Rechts Der Isar Hospital of the Technical University MunichDepartment of Neurology, Rechts Der Isar Hospital of the Technical University MunichNeuromuscular Diseases Center/ALS Clinic of the Kantonsspital StCentre de Reference SLA Et Autres Maladies du Neurone Moteur, Department of Neurology, CHRU BretonneauDepartment of Neurology and ALS Center, University of Miami Miller School of MedicineSchool of Medicine, Neurodegeneration Research Laboratory NDAL, Koç University, Research Center for Translational Medicine KUTTAMDepartment of Clinical Science, Neurosciences, Umeå UniversityBitcare GmbH, Technical University of MunichDepartment of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg UniversityDepartment of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology of the Polish Academy of SciencesMax Planck Institute for Biophysical Chemistry, Bioanalytical Mass SpectrometryFlinders Health and Medical Research Institute, College of Medicine and Public Health of the Flinders UniversityInstitute of Neuroimmunology, Slovak Academy of SciencesCentre de Reference SLA Et Autres Maladies du Neurone Moteur, Department of Neurology, CHRU BretonneauDepartment of Neurology, Hadassah University Hospital-Ein KeremNeuromuscular Diseases Center/ALS Clinic of the Kantonsspital StDepartment of Neurology, University Hospital MartinDepartment of Neurology, Akdeniz University HospitalDepartment of Neurology and ALS Center, University of Miami Miller School of MedicineDepartment of Computational Health, Helmholtz MunichDepartment of Neurology, Rechts Der Isar Hospital of the Technical University MunichAbstract Introduction The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need. Methods A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a presymptomatic and early ALS signature. Perspective The premodiALS study aim to identify a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early diagnosis and future clinical practice for ALS disease.https://doi.org/10.1186/s42466-025-00417-9Motoneuron diseasePre-symptomaticMulti-omicBiomarkersEarly diagnosisObservational study |
| spellingShingle | Laura Tzeplaeff Ana Galhoz Clara Meijs Lucas Caldi Gomes Andrej Kovac Amrei Menzel Hatice Değirmenci Abir Alaamel Hüseyin Can Kaya Ali Günalp Çelik Sine Dinçer Meltem Korucuk Sibel Berker Karaüzüm Elif Bayraktar Vildan Çiftçi Uğur Bilge Filiz Koç Antonia F. Demleitner Anne Buchberger Ricarda von Heynitz Vincent Gmeiner Christina Knellwolf Mohammed Mouzouri Joanne Wuu A. Nazli Başak Peter Munch Andersen Florian Kohlmayer Nicholas J. Ashton Wojciech Kuban Christof Lenz Mary-Louise Rogers Norbert Zilka Philippe Corcia Yossef Lerner Markus Weber Monika Turcanova Koprusakova Hilmi Uysal Michael Benatar Michael P. Menden Paul Lingor Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study Neurological Research and Practice Motoneuron disease Pre-symptomatic Multi-omic Biomarkers Early diagnosis Observational study |
| title | Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study |
| title_full | Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study |
| title_fullStr | Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study |
| title_full_unstemmed | Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study |
| title_short | Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study |
| title_sort | identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis als protocol of the premodials study |
| topic | Motoneuron disease Pre-symptomatic Multi-omic Biomarkers Early diagnosis Observational study |
| url | https://doi.org/10.1186/s42466-025-00417-9 |
| work_keys_str_mv | AT lauratzeplaeff identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT anagalhoz identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT clarameijs identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT lucascaldigomes identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT andrejkovac identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT amreimenzel identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT haticedegirmenci identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT abiralaamel identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT huseyincankaya identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT aligunalpcelik identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT sinedincer identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT meltemkorucuk identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT sibelberkerkarauzum identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT elifbayraktar identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT vildanciftci identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT ugurbilge identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT filizkoc identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT antoniafdemleitner identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT annebuchberger identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT ricardavonheynitz identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT vincentgmeiner identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT christinaknellwolf identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT mohammedmouzouri identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT joannewuu identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT anazlibasak identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT petermunchandersen identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT floriankohlmayer identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT nicholasjashton identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT wojciechkuban identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT christoflenz identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT marylouiserogers identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT norbertzilka identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT philippecorcia identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT yosseflerner identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT markusweber identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT monikaturcanovakoprusakova identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT hilmiuysal identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT michaelbenatar identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT michaelpmenden identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy AT paullingor identificationofapresymptomaticandearlydiseasesignatureforamyotrophiclateralsclerosisalsprotocolofthepremodialsstudy |