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This systematic review and meta-analysis analysed 97 studies, including 3212 patients with key ALS\/FTD gene mutations, to identify gene-specific behavioural profiles. Chromosome 9 open reading frame 72 (C9orf72) mutations were strongly associated with psychotic symptoms and aggression, while superoxide dismutase 1 (SOD1) mutations had minimal cognitive effects. Progranulin (PGRN) mutations correlated with apathy and hallucinations, microtubule-associated protein tau (MAPT) mutations with disinhibition, and charged multivesicular body protein 2B (CHMP2B) with social impairments. Fused in sarcoma (FUS) mutations caused early sleep disturbances, TANK-binding kinase 1 (TBK1) led to disinhibition, and presenilin 1 and 2 (PSEN1\/2) was linked to severe aggression. Prodromal cognitive changes in PGRN, MAPT, and CHMP2B mutations suggested early disease onset. Despite overlapping symptoms and clinical heterogeneity, understanding gene-specific patterns could inform tailored care strategies to enhance the quality of life for ALS and FTD patients. This study calls for refined guidelines integrating genetic behavioural profiles to improve patient and family support.<\/jats:p>","DOI":"10.3390\/ijms26136199","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Differential Effects of Genetic Mutations in ALS and FTD Genes on Behavioural and Cognitive Changes: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6400-3436","authenticated-orcid":false,"given":"Ana Maria","family":"Jim\u00e9nez-Garc\u00eda","sequence":"first","affiliation":[{"name":"BRABE Group, Department of Medicine and Health Sciences, Faculty of Life and Natural Sciences, University of Nebrija, C\/del Hostal, 28248 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eduarda","family":"Tortorella","sequence":"additional","affiliation":[{"name":"Institute Paulo Gontijo, R. 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Prado, 42-Indian\u00f3polis, S\u00e3o Paulo 04517-020, SP, Brazil"},{"name":"The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, 4 Newark St, London E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5602-5854","authenticated-orcid":false,"given":"Natalia","family":"Arias","sequence":"additional","affiliation":[{"name":"BRABE Group, Department of Medicine and Health Sciences, Faculty of Life and Natural Sciences, University of Nebrija, C\/del Hostal, 28248 Madrid, Spain"},{"name":"INEUROPA, Instituto de Neurociencias del Principado de Asturias, Faculty of Psychology, Plaza Feij\u00f3o s\/n, 33003 Oviedo, Spain"},{"name":"ISPA, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, Avenida Hospital Universitario s\/n, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.14336\/AD.2013.0400295","article-title":"Amyotrophic Lateral Sclerosis: An Update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials","volume":"4","author":"Gordon","year":"2013","journal-title":"Aging Dis."},{"key":"ref_2","first-page":"S65","article-title":"Frontotemporal Dementia: An Updated Overview","volume":"51","author":"Mohandas","year":"2009","journal-title":"Indian. J. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1093\/brain\/awac362","article-title":"Patients Carrying the Mutation p.R406W in MAPT Present with Non-Conforming Phenotypic Spectrum","volume":"146","author":"Gossye","year":"2023","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100607","DOI":"10.1016\/j.xcrm.2022.100607","article-title":"Comprehensive Cross-Sectional and Longitudinal Analyses of Plasma Neurofilament Light across FTD Spectrum Disorders","volume":"3","author":"Gendron","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ncl.2017.01.008","article-title":"Frontotemporal Dementia","volume":"35","author":"Olney","year":"2017","journal-title":"Neurol. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1093\/brain\/awr179","article-title":"Sensitivity of Revised Diagnostic Criteria for the Behavioural Variant of Frontotemporal Dementia","volume":"134","author":"Rascovsky","year":"2011","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1749-6632.2000.tb06904.x","article-title":"Classification and Description of Frontotemporal Dementias","volume":"920","author":"Neary","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jns.2017.02.061","article-title":"Screening for Cognitive and Behavioural Impairment in Amyotrophic Lateral Sclerosis: Frequency of Abnormality and Effect on Survival","volume":"376","author":"Xu","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/17482960701642437","article-title":"Behaviour in Amyotrophic Lateral Sclerosis","volume":"9","author":"Gibbons","year":"2008","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41398-020-01078-9","article-title":"Coexistence of Perseveration and Apathy in the TDP-43Q331K Knock-in Mouse Model of ALS\u2013FTD","volume":"10","author":"Kim","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1001\/2013.jamaneurol.181","article-title":"Distinct Clinical Characteristics of C9orf72 Expansion Carriers Compared with GRN, MAPT, and Nonmutation Carriers in a Flanders-Belgian FTLD Cohort","volume":"70","author":"Gijselinck","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/ana.21612","article-title":"TARDBP Mutations in Motoneuron Disease with Frontotemporal Lobar Degeneration","volume":"65","author":"Benajiba","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1136\/jnnp-2020-323969","article-title":"Cognition and Behaviour in Frontotemporal Dementia with and without Amyotrophic Lateral Sclerosis","volume":"91","author":"Saxon","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(16)00737-6","article-title":"The Frontotemporal Dementia-Motor Neuron Disease Continuum","volume":"388","author":"Burrell","year":"2016","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/cge.12973","article-title":"The Genotype-Phenotype Landscape of Familial Amyotrophic Lateral Sclerosis in Australia","volume":"92","author":"McCann","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/jmg.2010.077180","article-title":"SOD1, ANG, VAPB, TARDBP, and FUS Mutations in Familial Amyotrophic Lateral Sclerosis: Genotype-Phenotype Correlations","volume":"47","author":"Millecamps","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Connolly, O., Le Gall, L., McCluskey, G., Donaghy, C.G., Duddy, W.J., and Duguez, S. (2020). A Systematic Review of Genotype-Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS. J. Pers. Med., 10.","DOI":"10.3390\/jpm10030058"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3233\/JAD-132075","article-title":"Phenotypic Variability Associated with the C9ORF72 Hexanucleotide Repeat Expansion: A Sporadic Case of Frontotemporal Lobar Degeneration with Prodromal Hyposmia and Predominant Semantic Deficits","volume":"40","author":"Abbate","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1212\/WNL.0000000000004088","article-title":"CSF SAPP\u03b2, YKL-40, and Neurofilament Light in Frontotemporal Lobar Degeneration","volume":"89","author":"Alcolea","year":"2017","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3233\/JAD-2012-120523","article-title":"Early Onset Behavioral Variant Frontotemporal Dementia Due to the C9ORF72 Hexanucleotide Repeat Expansion: Psychiatric Clinical Presentations","volume":"31","author":"Arighi","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cortex.2021.03.006","article-title":"Recognition Memory and Divergent Cognitive Profiles in Prodromal Genetic Frontotemporal Dementia","volume":"139","author":"Barker","year":"2021","journal-title":"Cortex"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/brain\/awm320","article-title":"A Distinct Clinical, Neuropsychological and Radiological Phenotype Is Associated with Progranulin Gene Mutations in a Large UK Series","volume":"131","author":"Beck","year":"2008","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2030194","DOI":"10.1001\/jamanetworkopen.2020.30194","article-title":"Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia","volume":"4","author":"Benussi","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jagp.2015.04.007","article-title":"Frontotemporal Dementia and Psychiatric Illness: Emerging Clinical and Biological Links in Gene Carriers","volume":"24","author":"Block","year":"2016","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"fcad061","DOI":"10.1093\/braincomms\/fcad061","article-title":"Structural MRI Predicts Clinical Progression in Presymptomatic Genetic Frontotemporal Dementia: Findings from the GENetic Frontotemporal Dementia Initiative Cohort","volume":"5","author":"Bocchetta","year":"2023","journal-title":"Brain Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E974","DOI":"10.1002\/humu.21100","article-title":"Mutation within TARDBP Leads to Frontotemporal Dementia without Motor Neuron Disease","volume":"30","author":"Borroni","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_27","first-page":"625","article-title":"A Phenotype of Atypical Apraxia of Speech in a Family Carrying SQSTM1 Mutation","volume":"43","author":"Camuzat","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1007\/s00415-022-11068-0","article-title":"Anomia Is Present Pre-Symptomatically in Frontotemporal Dementia Due to MAPT Mutations","volume":"269","author":"Bouzigues","year":"2022","journal-title":"J. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1017\/S1041610217001193","article-title":"Rapidly Progressive Fronto-Temporal Dementia (FTD) Associated with Frontotemporal Lobar Degeneration (FTLD) in the Presence of Fused in Sarcoma (FUS) Protein: A Rare, Sporadic, and Aggressive Form of FTD","volume":"29","author":"Bradfield","year":"2017","journal-title":"Int. Psychogeriatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1002\/hbm.26220","article-title":"Cerebellar and Subcortical Atrophy Contribute to Psychiatric Symptoms in Frontotemporal Dementia","volume":"44","author":"Bussy","year":"2023","journal-title":"Hum. Brain Mapp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S1474-4422(12)70014-5","article-title":"Cognitive and Clinical Characteristics of Patients with Amyotrophic Lateral Sclerosis Carrying a C9orf72 Repeat Expansion: A Population-Based Cohort Study","volume":"11","author":"Byrne","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1007\/s11682-019-00253-x","article-title":"Temporal Variant of Frontotemporal Dementia in C9orf72 Repeat Expansion Carriers: Two Case Studies","volume":"14","author":"Caso","year":"2020","journal-title":"Brain Imaging Behav."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Castelnovo, V., Canu, E., Domi, T., Pozzi, L., Vignaroli, F., Spinelli, E.G., Ghirelli, A., Tondo, G., Comi, C., and Riva, N. (2023). A Novel GRN Mutation in an Italian Patient with Non-Fluent Variant of Primary Progressive Aphasia at Onset: A Longitudinal Case Report. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1204504"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1001\/jamaneurol.2015.4773","article-title":"The Role of APOE in the Occurrence of Frontotemporal Dementia in Amyotrophic Lateral Sclerosis","volume":"73","author":"Brunetti","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Christidi, F., Kleinerova, J., Tan, E.L., Delaney, S., Tacheva, A., Hengeveld, J.C., Doherty, M.A., McLaughlin, R.L., Hardiman, O., and Siah, W.F. (2024). Limbic Network and Papez Circuit Involvement in ALS: Imaging and Clinical Profiles in GGGGCC Hexanucleotide Carriers in C9orf72 and C9orf72-Negative Patients. Biology, 13.","DOI":"10.3390\/biology13070504"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8877","DOI":"10.1021\/acs.jafc.2c07606","article-title":"A Low-Protein, High-Carbohydrate Diet Exerts a Neuroprotective Effect on Mice with 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson\u2019s Disease by Regulating the Microbiota-Metabolite\u2013Brain Axis and Fibroblast Growth Factor 21","volume":"71","author":"Chu","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13195-021-00777-9","article-title":"Early Anterior Cingulate Involvement Is Seen in Presymptomatic MAPT P301L Mutation Carriers","volume":"13","author":"Clarke","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s00415-022-11433-z","article-title":"Motor, Cognitive and Behavioural Profiles of C9orf72 Expansion-Related Amyotrophic Lateral Sclerosis","volume":"270","author":"Colombo","year":"2023","journal-title":"J. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1001\/jamaneurol.2013.6002","article-title":"Frontotemporal Dementia Associated with the C9ORF72 Mutation: A Unique Clinical Profile","volume":"71","author":"Devenney","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.nicl.2016.11.028","article-title":"The Neural Correlates and Clinical Characteristics of Psychosis in the Frontotemporal Dementia Continuum and the C9orf72 Expansion","volume":"13","author":"Devenney","year":"2017","journal-title":"Neuroimage Clin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1002\/acn3.51363","article-title":"Neural Mechanisms of Psychosis Vulnerability and Perceptual Abnormalities in the ALS-FTD Spectrum","volume":"8","author":"Devenney","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3233\/JAD-220594","article-title":"Genetic Spectrum and Clinical Heterogeneity of Chinese Frontotemporal Dementia Patients: Data from PUMCH Dementia Cohort","volume":"89","author":"Dong","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1136\/jnnp-2013-306995","article-title":"Altered Body Schema Processing in Frontotemporal Dementia with C9ORF72 Mutations","volume":"85","author":"Downey","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1093\/brain\/awac446","article-title":"Neurodevelopmental Effects of Genetic Frontotemporal Dementia in Young Adult Mutation Carriers","volume":"146","author":"Finger","year":"2023","journal-title":"Brain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1136\/jnnp-2017-316799","article-title":"Longitudinal Diffusion Imaging across the C9orf72 Clinical Spectrum","volume":"89","author":"Floeter","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3109\/21678421.2014.959450","article-title":"Constructional Apraxia in Frontotemporal Dementia Associated with the C9orf72 Mutation: Broadening the Clinical and Neuropsychological Phenotype","volume":"16","author":"Floris","year":"2015","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cortex.2022.01.012","article-title":"Examining Empathy Deficits across Familial Forms of Frontotemporal Dementia within the GENFI Cohort","volume":"150","author":"Foster","year":"2022","journal-title":"Cortex"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Foxe, D., Elan, E., Burrell, J.R., Leslie, F.V.C., Devenney, E., Kwok, J.B., Halliday, G.M., Hodges, J.R., and Piguet, O. (2018). Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case Studies. Front. Psychol., 9.","DOI":"10.3389\/fpsyg.2018.01615"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3233\/JAD-2010-101413","article-title":"Intra-Familial Clinical Heterogeneity Due to FTLD-U with TDP-43 Proteinopathy Caused by a Novel Deletion in Progranulin Gene (PGRN)","volume":"22","author":"Gabryelewicz","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Rold\u00e1n, E., Rivas-Infante, E., Medina-Rodr\u00edguez, M., Arriola-Infante, J.E., Rodrigo-Herrero, S., Paradas, C., R\u00e1bano-Guti\u00e9rrez, A., and Franco-Mac\u00edas, E. (2023). Lessons Learned from a Sporadic FUSopathy in a Young Man: A Case Report. BMC Neurol., 23.","DOI":"10.1186\/s12883-023-03082-0"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1136\/practneurol-2020-002730","article-title":"Young-Onset Frontotemporal Dementia with FUS Pathology","volume":"21","author":"Gowell","year":"2020","journal-title":"Pract. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gramaglia, C., Cantello, R., Terazzi, E., Carecchio, M., D\u2019Alfonso, S., Chieppa, N., Ressico, F., Rizza, M.C., and Zeppegno, P. (2014). Early Onset Frontotemporal Dementia with Psychiatric Presentation Due to the C9ORF72 Hexanucleotide Repeat Expansion: A Case Report. BMC Neurol., 14.","DOI":"10.1186\/s12883-014-0228-6"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/alz.12046","article-title":"Comparison of Sporadic and Familial Behavioral Variant Frontotemporal Dementia (FTD) in a North American Cohort","volume":"16","author":"Heuer","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/13554794.2021.1918723","article-title":"Underlying Pathology Identified after 20 Years of Disease Course in Two Cases of Slowly Progressive Frontotemporal Dementia Syndromes","volume":"27","author":"Hokelekli","year":"2021","journal-title":"Neurocase"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e141","DOI":"10.1212\/WNL.0000000000011093","article-title":"Differential Neuropsychological Profile of Patients With Amyotrophic Lateral Sclerosis With and Without C9orf72 Mutation","volume":"96","author":"Iazzolino","year":"2021","journal-title":"Neurology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1007\/s00415-023-11845-5","article-title":"Longitudinal Changes in Qualitative Aspects of Semantic Fluency in Presymptomatic and Prodromal Genetic Frontotemporal Dementia","volume":"270","author":"Jiskoot","year":"2023","journal-title":"J. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/WNN.0000000000000008","article-title":"Psychosis and Hallucinations in Frontotemporal Dementia with the C9ORF72 Mutation: A Detailed Clinical Cohort","volume":"26","author":"Kertesz","year":"2013","journal-title":"Cogn. Behav. Neurol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00415-002-0687-3","article-title":"Contrasting Genotypes of the Tau Gene in Two Phenotypically Distinct Patients with P301L Mutation of Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17","volume":"249","author":"Kobayashi","year":"2002","journal-title":"J. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kobayashi, R., Naruse, H., Kawakatsu, S., Iseki, C., Suzuki, Y., Koyama, S., Morioka, D., Ishiura, H., Mitsui, J., and Ohta, Y. (2022). Valosin-Containing Protein Asp395Gly Mutation in a Patient with Frontotemporal Dementia: A Case Report. BMC Neurol., 22.","DOI":"10.1186\/s12883-022-02951-4"},{"key":"ref_60","first-page":"75","article-title":"The Clinical, Neuroanatomical, and Neuropathologic Phenotype of TBK1-Associated Frontotemporal Dementia: A Longitudinal Case Report","volume":"6","author":"Koriath","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/neup.12233","article-title":"Clinicopathological Description of Two Cases with SQSTM1 Gene Mutation Associated with Frontotemporal Dementia","volume":"36","author":"Kovacs","year":"2016","journal-title":"Neuropathology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s40478-022-01455-z","article-title":"Synaptic Proteomics Reveal Distinct Molecular Signatures of Cognitive Change and C9ORF72 Repeat Expansion in the Human ALS Cortex","volume":"10","author":"Laszlo","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1177\/08919887231195337","article-title":"Atypical Neuropsychiatric Presentation of FTD-ALS Caused by a Pathogenic Repeat Expansion in C9orf72: A Case Report","volume":"37","author":"LeBlanc","year":"2024","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/brain\/awu248","article-title":"Altered Network Connectivity in Frontotemporal Dementia with C9orf72 Hexanucleotide Repeat Expansion","volume":"137","author":"Lee","year":"2014","journal-title":"Brain"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1176\/appi.neuropsych.18050114","article-title":"Bifrontal Hypermetabolism on Brain FDG-PET in a Case of C9orf72-Related Behavioral Variant of Frontotemporal Dementia","volume":"31","author":"Levy","year":"2019","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/brain\/awr361","article-title":"Frontotemporal Dementia with the C9ORF72 Hexanucleotide Repeat Expansion: Clinical, Neuroanatomical and Neuropathological Features","volume":"135","author":"Mahoney","year":"2012","journal-title":"Brain"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Manini, A., Casiraghi, V., Brusati, A., Maranzano, A., Gentile, F., Colombo, E., Bonetti, R., Peverelli, S., Invernizzi, S., and Gentilini, D. (2023). Association of the Risk Factor UNC13A with Survival and Upper Motor Neuron Involvement in Amyotrophic Lateral Sclerosis. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1067954"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1212\/WNL.0b013e318251594c","article-title":"Similar Clinical and Neuroimaging Features in Monozygotic Twin Pair with Mutation in Progranulin","volume":"78","author":"McDade","year":"2012","journal-title":"Neurology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/21678421.2021.1903505","article-title":"Early Juvenile Reading Epilepsy and Later Frontotemporal Dementia (FTD): Expanding the Clinical Phenotype of C9ORF72 Mutation?","volume":"23","author":"Melis","year":"2022","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2147\/NDT.S156084","article-title":"Manic Behavior and Asymmetric Right Frontotemporal Dementia from a Novel Progranulin Mutation","volume":"14","author":"Mendez","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/23279095.2020.1716357","article-title":"A Modified Camel and Cactus Test Detects Presymptomatic Semantic Impairment in Genetic Frontotemporal Dementia within the GENFI Cohort","volume":"29","author":"Moore","year":"2022","journal-title":"Appl. Neuropsychol. Adult"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/acn3.51544","article-title":"The CBI-R Detects Early Behavioural Impairment in Genetic Frontotemporal Dementia","volume":"9","author":"Nelson","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1136\/jmg-2022-108627","article-title":"Frontotemporal Dementia Presentation in Patients with Heterozygous p.H157Y Variant of TREM2","volume":"60","author":"Ogonowski","year":"2023","journal-title":"J. Med. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jalz.2019.08.196","article-title":"Clinical and Volumetric Changes with Increasing Functional Impairment in Familial Frontotemporal Lobar Degeneration","volume":"16","author":"Olney","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s12311-018-0998-2","article-title":"Autosomal Dominant Gene Negative Frontotemporal Dementia-Think of SCA17","volume":"18","author":"Olszewska","year":"2019","journal-title":"Cerebellum"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1136\/jnnp-2021-326868","article-title":"Comparison of Clinical Rating Scales in Genetic Frontotemporal Dementia within the GENFI Cohort","volume":"93","author":"Peakman","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5281","DOI":"10.1007\/s10072-022-06185-7","article-title":"Sex Influences Clinical Phenotype in Frontotemporal Dementia","volume":"43","author":"Pengo","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Pletnikova, O., Sloane, K.L., Renton, A.E., Traynor, B.J., Crain, B.J., Reid, T., Zu, T., Ranum, L.P.W., Troncoso, J.C., and Rabins, P.V. (2014). Hippocampal Sclerosis Dementia with the C9ORF72 Hexanucleotide Repeat Expansion. Neurobiol. Aging, 35.","DOI":"10.1016\/j.neurobiolaging.2014.04.009"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1007\/s00415-020-09738-y","article-title":"Cognitive Profiles Discriminate between Genetic Variants of Behavioral Frontotemporal Dementia","volume":"267","author":"Poos","year":"2020","journal-title":"J. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e281","DOI":"10.1212\/WNL.0000000000200384","article-title":"Longitudinal Cognitive Changes in Genetic Frontotemporal Dementia Within the GENFI Cohort","volume":"99","author":"Poos","year":"2022","journal-title":"Neurology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cortex.2020.08.023","article-title":"Social Cognition Impairment in Genetic Frontotemporal Dementia within the GENFI Cohort","volume":"133","author":"Russell","year":"2020","journal-title":"Cortex"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1007\/s00415-022-11512-1","article-title":"Language Impairment in the Genetic Forms of Behavioural Variant Frontotemporal Dementia","volume":"270","author":"Samra","year":"2023","journal-title":"J. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1136\/jnnp-2022-330152","article-title":"Neuropsychiatric Symptoms in Genetic Frontotemporal Dementia: Developing a New Module for Clinical Rating Scales","volume":"94","author":"Samra","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Santamar\u00eda-Garc\u00eda, H., Ogonowsky, N., Baez, S., Palacio, N., Reyes, P., Schulte, M., L\u00f3pez, A., Matallana, D., and Ibanez, A. (2022). Neurocognitive Patterns across Genetic Levels in Behavioral Variant Frontotemporal Dementia: A Multiple Single Cases Study. BMC Neurol., 22.","DOI":"10.1186\/s12883-022-02954-1"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sassi, C., Capozzo, R., Hammer, M., Zecca, C., Federoff, M., Blauwendraat, C., Bernstein, N., Ding, J., Gibbs, J.R., and Price, T. (2021). Exploring Dementia and Neuronal Ceroid Lipofuscinosis Genes in 100 FTD-like Patients from 6 Towns and Rural Villages on the Adriatic Sea Cost of Apulia. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85494-x"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/brain\/awac043","article-title":"Psychiatric Symptoms of Frontotemporal Dementia and Subcortical (Co-)Pathology Burden: New Insights","volume":"146","author":"Scarioni","year":"2023","journal-title":"Brain"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1136\/jnnp-2022-328921","article-title":"Genotype-Phenotype Correlations in Valosin-Containing Protein Disease: A Retrospective Muticentre Study","volume":"93","author":"Schiava","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1212\/WNL.0b013e3182270456","article-title":"Brain Perfusion Patterns in Familial Frontotemporal Lobar Degeneration","volume":"77","author":"Seelaar","year":"2011","journal-title":"Neurology"},{"key":"ref_89","first-page":"147","article-title":"Distinct Neuroanatomical Correlates of Neuropsychiatric Symptoms in the Three Main Forms of Genetic Frontotemporal Dementia in the GENFI Cohort","volume":"65","author":"Sellami","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/0891988714554710","article-title":"Clinicopathological Study of Patients With C9ORF72-Associated Frontotemporal Dementia Presenting With Delusions","volume":"28","author":"Shinagawa","year":"2015","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/ene.15058","article-title":"Serum Neurofilament Light Chain as a Surrogate of Cognitive Decline in Sporadic and Familial Frontotemporal Dementia","volume":"29","author":"Lima","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1093\/brain\/awl267","article-title":"Progranulin Gene Mutations Associated with Frontotemporal Dementia and Progressive Non-Fluent Aphasia","volume":"129","author":"Snowden","year":"2006","journal-title":"Brain"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00401-011-0816-0","article-title":"The Most Common Type of FTLD-FUS (AFTLD-U) Is Associated with a Distinct Clinical Form of Frontotemporal Dementia but Is Not Related to Mutations in the FUS Gene","volume":"122","author":"Snowden","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Solje, E., Aaltokallio, H., Koivumaa-Honkanen, H., Suhonen, N.M., Moilanen, V., Kiviharju, A., Traynor, B., Tienari, P.J., Hartikainen, P., and Remes, A.M. (2015). The Phenotype of the C9ORF72 Expansion Carriers According to Revised Criteria for BvFTD. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131817"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Spinelli, E.G., Ghirelli, A., Riva, N., Canu, E., Castelnovo, V., Domi, T., Pozzi, L., Carrera, P., Silani, V., and Chi\u00f2, A. (2022). Profiling Morphologic MRI Features of Motor Neuron Disease Caused by TARDBP Mutations. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.931006"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1038\/s41591-022-01942-9","article-title":"Temporal Order of Clinical and Biomarker Changes in Familial Frontotemporal Dementia","volume":"28","author":"Staffaroni","year":"2022","journal-title":"Nat. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/ana.25841","article-title":"The Distinct Traits of the UNC13A Polymorphism in Amyotrophic Lateral Sclerosis","volume":"88","author":"Tan","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000058328","article-title":"Familial Frontotemporal Dementia Associated with a Novel Presenilin-1 Mutation","volume":"14","author":"Lewis","year":"2002","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e2439","DOI":"10.1002\/brb3.2439","article-title":"Loss of \u201cInsight\u201d into Behavioral Changes in ALS: Differences across Cognitive Profiles","volume":"12","author":"Temp","year":"2022","journal-title":"Brain Behav."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e1154","DOI":"10.1212\/WNL.0000000000200860","article-title":"Differences in Motor Features of C9orf72, MAPT, or GRN Variant Carriers With Familial Frontotemporal Lobar Degeneration","volume":"99","author":"Tipton","year":"2022","journal-title":"Neurology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"103222","DOI":"10.1016\/j.nicl.2022.103222","article-title":"Clinical Relevance of Single-Subject Brain Metabolism Patterns in Amyotrophic Lateral Sclerosis Mutation Carriers","volume":"36","author":"Tondo","year":"2022","journal-title":"Neuroimage Clin."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1001\/archneur.64.8.1148","article-title":"Clinical, Genetic, and Pathologic Characteristics of Patients with Frontotemporal Dementia and Progranulin Mutations","volume":"64","author":"Wood","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Vinceti, G., Gallingani, C., Zucchi, E., Martinelli, I., Gianferrari, G., Simonini, C., Bedin, R., Chiari, A., Zamboni, G., and Mandrioli, J. (2023). Young Onset Alzheimer\u2019s Disease Associated with C9ORF72 Hexanucleotide Expansion: Further Evidence for a Still Unsolved Association. Genes, 14.","DOI":"10.3390\/genes14040930"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wang, Y., Duan, X., Zhou, X., Wang, R., Zhang, X., Cao, Z., Wang, X., Zhou, Z., Sun, Y., and Peng, D. (2022). ANXA11 Mutations Are Associated with Amyotrophic Lateral Sclerosis-Frontotemporal Dementia. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.886887"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s00415-009-0078-0","article-title":"SOD1 and Cognitive Dysfunction in Familial Amyotrophic Lateral Sclerosis","volume":"256","author":"Wicks","year":"2009","journal-title":"J. Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"fcad087","DOI":"10.1093\/braincomms\/fcad087","article-title":"Clinical and Genetic Features of Amyotrophic Lateral Sclerosis Patients with C9orf72 Mutations","volume":"5","author":"Wiesenfarth","year":"2023","journal-title":"Brain Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ana.26265","article-title":"Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and PNfH: A Longitudinal Multicentre Study","volume":"91","author":"Wilke","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/nan.12247","article-title":"Slowly Progressive Behavioural Presentation in Two UK Cases with the R406W MAPT Mutation","volume":"42","author":"Wood","year":"2016","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1186\/s13023-022-02531-2","article-title":"Mutation Spectrum of Chinese Amyotrophic Lateral Sclerosis Patients with Frontotemporal Dementia","volume":"17","author":"Yang","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1002\/ana.25739","article-title":"Frontotemporal Dementia: Correlations Between Psychiatric Symptoms and Pathology","volume":"87","author":"Scarioni","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Kobayashi, Y., Sugahara, H., Shimada, K., Mitsuyama, E., Kuhara, T., Yasuoka, A., Kondo, T., Abe, K., and Xiao, J. (2017). Therapeutic Potential of Bifidobacterium Breve Strain A1 for Preventing Cognitive Impairment in Alzheimer\u2019s Disease. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-13368-2"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:02Z","timestamp":1760032802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":111,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136199"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136199","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}