Aspetti genetici e biomarcatori nella demenza frontotemporale: stato dell’arte e prospettive future.
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Contenuto principale dell'articolo
Abstract
Introduzione
La demenza frontotemporale (FTD) rappresenta la terza demenza più comune dopo quella di Alzheimer e a Corpi di Levy. Colpisce la corteccia dei lobi frontali e temporali, è ad esordio precoce e, secondo l’ultimo criterio, è classificata in variante comportamentale e afasia progressiva primaria, quest’ultima a sua volta diversificata in tre sottotipi: semantica, non fluente e logopenica.
Il 30-50% è di origine familiare con diverse mutazioni genetiche identificate. I meccanismi patologici alla base della FTD sono altamente eterogenei ma le cause più comuni sono le proteinopatie TDP-43 e le tauopatie.
La diagnosi è ancora difficile e si basa su criteri clinici e neuroradiologici.
Anche se non esiste alcun biomarcatore specifico, sono in corso intensi sforzi per sviluppare un nuovo approccio alla diagnosi e alla valutazione della progressione clinica nella FTD, attraverso un modello multimodale di biomarcatori di fluido (liquido cerebrospinale e plasma/siero), avvalendosi di nuovi dispositivi, Lab-on-Chip, per la rilevazione immunometrica e molecolare di specifici analiti.
Obiettivo
Fornire uno stato dell’arte sulla patogenesi della FTD, partendo dai risultati consolidati ed integrandoli con quelli più recenti, alla luce dei criteri diagnostici con particolare riguardo ai biomarcatori su fluidi biologici, attraverso l’uso di dispositivi miniaturizzati.
Metodologia
Sono stati esaminati i progressi nel campo della genetica, valutandoli in relazione sia alle manifestazioni cliniche che ai risultati istopatologici; inoltre sono stati esplorati gli attuali criteri diagnostici con particolare riguardo ai biomarcatori su fluidi biologici.
Risultati
Dall’analisi dei dati reperibili in letteratura è emerso che la diagnosi di FTD è difficile, soprattutto nelle fasi iniziali, a causa dell’assenza di segni e sintomi clinici specifici.
In questo contesto, la medicina di laboratorio, attraverso la ricerca di biomarcatori su fluidi biologici anche tramite i dispositivi miniaturizzati Lab-on-Chip, può rivestire un ruolo di notevole importanza nel rilevare e differenziare i disturbi neurodegenerativi.
Conclusioni
I dati reperiti in letteratura confermano che i biomarcatori possono indicare i meccanismi patologici alla base della FTD e, a tal riguardo, sono in corso intensi sforzi per introdurre metodi analitici ad alta sensibilità, come l’utilizzo multimodale di biomarcatori di fluido, avvalendosi di nuovi dispositivi, i Lab-on-Chip, per la rilevazione immunometrica e molecolare di specifici analiti.
Tali dispositivi miniaturizzati offrono la soluzione per condurre analisi biologiche e biochimiche su più campioni in un’unica piattaforma, comportando una riduzione dei costi, aumento della velocità e della sensibilità, nonché una maggiore accuratezza diagnostica.
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Riferimenti bibliografici
[1] Olney, N.T.; Spina, S.; Miller, B.L. Frontotemporal Dementia. Neurol. Clin. 2017, 35, 339–374.
[2] Mesulam,M.M.; Wieneke,C.; Thompson, C.; Rogalski, E.;Weintraub, S. Quantitative classification of primary progressive aphasiaat early and mild impairment stages. Brain 2012, 135 Pt 5, 1537–1553.
[3] Brun A. Identification and Characterization of Frontal Lobe Degeneration: Historical perspective on the development of FTD. Alzheimer Dis. Assoc. Disord. 2007;21:S3–S4. doi: 10.1097/WAD.0b013e31815bf511.
[4] Logroscino, G.; Piccininni, M.; Graff, C.; Hardiman, O.; Ludolph, A.C.; Moreno, F.; Otto, M.; Remes, A.M.; Rowe, J.B.; Seelaar, H.; et al. Incidence of Syndromes Associated with Frontotemporal Lobar Degeneration in 9 European Countries. JAMA Neurol. 2023, 80, 279–286.
[5] Logroscino G., Piccininni M, Binetti G., Zecca C., et al. Incidence of frontotemporal lobar degeneration in Italy: the Salento-Brescia Registry study. Neurology 2019;92: e2355-e2363. Doi: 10,1212/WNL.0000000000007498.
[6] Young J.J., Lavakumar M., Tampi D., Balachandran S., Tampi R.R. Frontotemporal dementia: Latest evidence and clinical implications. Ther. Adv. Psychopharmacol. 2018;8:33–48. doi: 10.1177/2045125317739818.
[7] Arvanitakis Z. Update on frontotemporal dementia. Neurologist. 2010;16:16–22. doi: 10.1097/NRL.0b013e3181b1d5c6.
[8] Onyike, C.U.; Diehl-Schmid, J. The epidemiology of frontotemporal dementia. Int. Rev. Psychiatry 2013, 25, 130–137.
[9] Sosa-Ortiz, A.L.; Acosta-Castillo, I.; Prince, M.J. Epidemiology of Dementias and Alzheimer’s Disease. Arch. Med. Res. 2012, 43,600–608.
[10] Coyle-Gilchrist, I.T.; Dick, K.M.;Patterson, K.; Vázquez Rodríquez, P.; Wehmann, E.;Wilcox, A.; Lansdall, C.J.; Dawson, K.E.;Wiggins, J.; Mead, S.; et al. Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology 2016, 86, 1736–1743.
[11] Neumann, M.; Kwong, L.K.; Truax, A.C.; Vanmassenhove, B.; Kretzschmar, H.A.; Van Deerlin, V.M.; Clark, C.M.; Grossman,M.; Miller, B.L.; Trojanowski, J.Q.; et al. TDP-43-Positive White Matter Pathology in Frontotemporal Lobar DegenerationWithUbiquitin-Positive Inclusions. J. Neuropathol. Exp. Neurol. 2007, 66, 177–183.
[12] Erkkinen, M.G.; Kim, M.O.; Geschwind, M.D. Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases.Cold Spring Harb. Perspect. Biol. 2018, 10, a033118. Doi:10.1101/cshperspect.a033118.
[13] Piguet O, Hornberger M, Mioshi E, Hodges JR: Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol 2011, 10:162–172. doi: 10.1016/S1474-4422(10)70299-4.
[14] Lillo P, Garcin B, Hornberger M, Bak TH, Hodges JR: Neurobehavioralfeatures in frontotemporal dementia with amyotrophic lateral sclerosis. Arch Neurol 2010, 67:826–830.
[15] Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, et al: Sensitivity ofrevised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011, 134:2456–2477.
[16] Younes K, Borghesani V, Montembeault M, Spina S, Mandelli ML, Welch AE, Weis E, Callahan P, Elahi FM, Hua AY. Right temporal degenerationand socioemotional semantics: semantic behavioural variant frontotemporal dementia. Brain 2022; 145(11), 4080-4096.
[17] Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M.: Classification of primary progressive aphasia and its variants. Neurology2011;76(11),1006-1014 doi.org/10.1212/WNL.0b013e31821103e6
[18] Aiba I, Hayashi Y, Shimohata T, Yoshida M, Saito Y, Wakabayashi K, Komori T, Hasegawa M, Ikeuchi T, Tokumaru AM. Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome. Brain 2023; Communications, 5(6), fcad296.
[19] Strong MJ, Abrahams S, Goldstein LH, Woolley S, Mclaughlin P, Snowden J, Mioshi E, Roberts-South A, Benatar M, HortobáGyi T. Amyotrophiclateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2017; 18(3-4), 153-174.
[20] Ikeda M, Ishikawa T, Tanabe H: Epidemiology of frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 2004, 17:265–268.
[21] van Langenhove T, van der Zee J, van Broeckhoven C: The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann Med 2012, 44:817–828
[22] The Lund and Manchester Groups: Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 1994, 57:416–418.
[23] Rohrer JD, Lashley T, Schott JM, Warren JE, Mead S, Isaacs AM, Beck J, HardyJ, de Silva R, Warrington E, et al: Clinical and neuroanatomical signaturesof tissue pathology in frontotemporal lobar degeneration. Brain 2011,134:2565–2581.
[24] Grossman M: Primary progressive aphasia: clinicopathologicalcorrelations. Nat Rev Neurol 2010, 6:88–97.
[25] Irwin DJ, McMillan CT, Toledo JB, Arnold SE, Shaw LM, Wang LS, Van Deerlin V,Lee VM, Trojanowski JQ, Grossman M: Comparison of cerebrospinal fluidlevels of tau and Abeta 1-42 in Alzheimer disease and frontotemporaldegeneration using 2 analytical platforms. Arch Neurol 2012, 69:1018–1025.
[26] Verwey NA, Kester MI, van der Flier WM, Veerhuis R, Berkhof H, TwaalfhovenH, Blankenstein MA, Scheltens AP, Pijnenburg YA: Additional value of CSF amyloid-beta 40 levels in the differentiation between FTLD and controlsubjects. J Alzheimers Dis 2010, 20:445–452.
[27] Snowden JS, Thompson JC, Stopford CL, Richardson AM, Gerhard A, Neary D, Mann DM: The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships. Brain 2011, 134:2478–2492.
[28] Mackenzie IR, Foti D, Woulfe J, Hurwitz TA: Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions. Brain 2008, 131:1282–1293.
[29] Josephs KA, Hodges JR, Snowden JS, Mackenzie IR, Neumann M, Mann DM,Dickson DW: Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol 2011, 122:137–153.
[30] Gorno-Tempini ML, Brambati SM, Ginex V, Ogar J, Dronkers NF, Marcone A, Perani D, Garibotto V, Cappa SF, Miller BL: The logopenic/phonological variant of primary progressive aphasia. Neurology 2008, 71:1227–1234.
[31] Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, Cowie TF, Dickinson KL, Maruff P, Darby D, et al: Imaging beta-amyloid burden in aging and dementia. Neurology 2007, 68:1718–1725.
[32] Mesulam M, Wicklund A, Johnson N, Rogalski E, Leger GC, Rademaker A, Weintraub S, Bigio EH: Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008, 63:709–719.
[33] Rabinovici GD, Jagust WJ, Furst AJ, Ogar JM, Racine CA, Mormino EC, O’Neil JP, Lal RA, Dronkers NF, Miller BL, et al: Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 2008, 64:388–401.
[34] Phukan J, Pender NP, Hardiman O: Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol 2007, 6:994–1003.
[35] Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE: Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 2005, 65:586–590.
[36] Rogers Brian S. & Lippa Carol F. A Clinical Approach to Early-Onset Inheritable Dementia. American Journal of Alzheimer's Disease&Other Dementias®Volume 27,
Issue 3, May2012, Pages 154-161. https://doi.org/10.1177/1533317512444000.
[37] Brun, A. Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology. Arch. Gerontol. Geriatr. 1987, 6, 193–208.
[38] Jones, D.T.; Knopman, D.S.; Graff-Radford, J.; Syrjanen, J.A.; Senjem, M.L.; Schwarz, C.G.; Dheel, C.; Wszolek, Z.; Rademakers, R.;Kantarci, K.; et al. In vivo 18F-AV-1451 tau PET signal in MAPT mutation carriers varies by expected tau isoforms. Neurology 2018, 90, e947–e954.
[39] Kurtishi, A.; Rosen, B.; Patil, K.S.; Alves, G.W.; Møller, S.G. Cellular Proteostasis in Neurodegeneration. Mol. Neurobiol. 2019, 56,3676–3689.
[40] Beckers, J.; Tharkeshwar, A.K.; Van Damme, P. C9orf72 ALS-FTD: Recent evidence for dysregulation of the autophagy-lysosomepathway at multiple levels. Autophagy 2021, 17, 3306–3322.
[41] Lines, G.; Casey, J.M.; Preza, E.; Wray, S. Modelling frontotemporal dementia using patient-derived induced pluripotent stecells. Mol. Cell. Neurosci. 2020, 109, 103553.
[42] Gao, J.; Wang, L.; Yan, T.; Perry, G.; Wang, X. TDP-43 proteinopathy and mitochondrial abnormalities in neurodegeneration. Mol.Cell. Neurosci. 2019, 100, 103396.
[43] Houghton, O.H.; Mizielinska, S.; Gomez-Suaga, P. The Interplay Between Autophagy and RNA Homeostasis: Implications forAmyotrophic Lateral Sclerosis and Frontotemporal Dementia. Front. Cell Dev. Biol. 2022, 10, 838402.
[44] Gomez-Suaga, P.; Mórotz, G.M.; Markovinovic, A.; Martín-Guerrero, S.M.; Preza, E.; Arias, N.; Mayl, K.; Aabdien, A.; Gesheva, V. Nishimura, A.; et al. Disruption of ER-mitochondria tethering and signalling in C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia. Aging Cell 2022, 21, e13549.
[45] Neumann, M.; MacKenzie, I.R.A. Review: Neuropathology of non-tau frontotemporal lobar degeneration. Neuropathol.Appl. Neurobiol.2019,45,19–40.
[46] Perry, D.C.; Brown, J.A.; Possin, K.L.; Datta, S.; Trujillo, A.; Radke, A.; Karydas, A.; Kornak, J.; Sias, A.C.; Rabinovici, G.D.; et al. Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain 2017, 140, 3329–3345.
[47] Seeley W.W., Crawford R., Rascovsky K., Kramer J.H., Weiner M., Miller B.L., Gorno-Tempini M.L. Frontal Paralimbic Network Atrophy in Very Mild Behavioral Variant Frontotemporal Dementia. Arch. Neurol. 2008;65:249–255. doi: 10.1001/archneurol.2007.38.
[48] Tan, R.H.; Wong, S.; Kril, J.J.; Piguet, O.; Hornberger, M.; Hodges, J.R.; Halliday, G.M. Beyond the temporal pole: Limbic memory circuit in the semantic variant of primary progressive aphasia. Brain2014,137 Pt7,2065–2076.
[49] Gelpi, E.; van der Zee, J.; Turon Estrada, A.; Van Broeckhoven, C.; Sanchez- Valle, R. TARDBP mutationp. Ile383Val associated with semantic dementia and complex proteinopathy. Neuropathol. Appl. Neurobiol. 2014, 40, 225–230.
[50] Josephs KA, Whitwell JL, Duffy JR, Vanvoorst WA, Strand EA, Hu WT, Boeve BF, Graff-Radford NR, Parisi JE, Knopman DS, et al: Progressive aphasia secondary to Alzheimer disease vs FTLD pathology. Neurology 2008, 70:25–34
[51] Ulugut Erkoyun, H.; Groot, C.; Heilbron, R.; Nelissen, A.; van Rossum, J.; Jutten, R.; Koene,T.;van der Flier, W.M.; Wattjes, M.P.;Scheltens, P.; et al. A clinical-radiological framework of the right temporal variant of frontotemporal dementia. Brain 2020, 143,2831–2843.
[52] Rogers Brian S. & Lippa Carol F.. A Clinical Approach to Early-Onset Inheritable Dementia. American Journal of Alzheimer's Disease&Other Dementias®Volume 27,
Issue 3, May2012, Pages 154-161.https://doi.org/10.1177/1533317512444000
[53] Grossman M, Seeley WW, Boxer AL, et al. Frontotemporal lobar degeneration. Nat Rev Dis Primers. 2023 Aug 10; 9(1): 40.
[54] Hulya Ulugut, Yolande A. L. Pijnenburg. Frontotemporal dementia: Past, present, and future First published: 28 June Alzheimer e demenza Volume 19, Issue 11 p. 5253-5263/ / 2023https://doi.org/10.1002/alz.13363
[55] Fenoglio, C.; Scarpini, E.; Serpente, M.; Galimberti, D. Role of Genetics and Epigenetics in the Pathogenesis of Alzheimer’s Disease and Frontotemporal Dementia. J. Alzheimer’s Dis. 2018, 62, 913–932.
[56] Borroni, B.; Bonvicini, C.; Galimberti, D.; Tremolizzo, L.; Papetti, A.; Archetti, S.; Turla, M.; Alberici, A.; Agosti, C.; Premi, E.; et al.Founder effect and estimation of the age of the Progranulin Thr272fs mutation in 14 Italian pedigrees with frontotemporal lobardegeneration. Neurobiol. Aging 2011, 32, 555.e1–555.e8.
[57] Barandiaran, M.; Estanga, A.; Moreno, F.; Indakoetxea, B.; Alzualde, A.; Balluerka, N.; Martí Massó, J.F.; López de Munain, A.Neuropsychological Features of Asymptomatic c.709-1G>A Progranulin Mutation Carriers. J. Int. Neuropsychol. Soc. 2012, 18,1086–1090.
[58] Floris, G.; Borghero, G.; Cannas, A.; Di Stefano, F.; Murru, M.R.; Corongiu, D.; Cuccu, S.; Tranquilli, S.; Cherchi, M.V.;Serra, A.; et al. Clinical phenotypes and radiological findings in frontotemporal dementia related to TARDBP mutations. J.Neurol. 2015, 262, 375–384.
[59] Greaves, C.V.; Rohrer, J.D. An update on genetic frontotemporal dementia. J. Neurol. 2019, 266, 2075–2086.
[60] Snowden, J.S.; Adams, J.; Harris, J.; Thompson, J.C.; Rollinson, S.; Richardson, A.; Jones, M.; Neary, D.; Mann, D.M.; Pickering-Brown, S. Distinctclinicaland pathological phenotypes in frontotemporal dementia associated with MAPT, PGRN and C9orf72mutations. Amyotroph. Lateral Scler. Front. Degener. 2015, 16, 497–505.
[61] Convery R, Mead S, Rohrer JD. Review: Clinical, genetic and neuroimaging features of frontotemporal dementia. Neuropathol Appl Neurobiol.2019 Feb; 45(1): 6-18.
[62] Paushter, D.H.; Du, H.; Feng, T.; Hu, F. The lysosomal function of progranulin, a guardian against neurodegeneration. ActaNeuropathol. 2018, 136, 1–17.
[63] Yu, C.-E.; Bird, T.D.; Bekris, L.M.; Montine, T.J.; Leverenz, J.B.; Steinbart, E.; Galloway, N.M.; Feldman, H.; Woltjer, R.;Miller, C.A.; et al. The Spectrum of Mutations in Progranulin: A collaborative study screening 545 cases of neurodegeneration.Arch. Neurol. 2010, 67, 161–170.
[64] Boland, S.; Swarup, S.; Ambaw, Y.A.; Malia, P.C.; Richards, R.C.; Fischer, A.W.; Singh, S.; Aggarwal, G.; Spina, S.; Nana, A.L.; et al. Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis. Nat. Commun. 2022, 13, 5924.
[65] Bright, F.; Werry, E.L.; Dobson-Stone, C.; Piguet, O.; Ittner, L.M.; Halliday, G.M.; Hodges, J.R.; Kiernan, M.C.; Loy, C.T.; Kassiou, M.; et al. Neuroinflammation in frontotemporal dementia. Nat. Rev. Neurol. 2019, 15, 540–555.
[66] Wang, Y.; Mandelkow, E. Tau in physiology and pathology. Nat. Rev. Neurosci. 2016, 17, 22–35.
[67] Lines, G.; Casey, J.M.; Preza, E.; Wray, S. Modelling frontotemporal dementia using patient-derived induced pluripotent stecells. Mol. Cell. Neurosci. 2020, 109, 103553.
[68] Rovelet-Lecrux, A.; Hannequin, D.; Guillin, O.; Legallic, S.; Jurici, S.; Wallon, D.; Frebourg, T.; Campion, D. FrontotemporalDementia Phenotype Associated with MAPT Gene Duplication. J. Alzheimer’s Dis. 2010, 21, 897–902.
[69] Benussi, A.; Epadovani, A.; Eborroni, B. Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia. Front. Aging Neurosci.2015, 7, 171.
[70] Watts GD, Wymer J, Kovach MJ, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004 Apr; 36(4): 377-381.
[71] Skibinski G, Parkinson NJ, Brown JM, et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. NatGenet.2005 Aug; 37(8): 806-808.
[72] Rubino E, Rainero I, Chiò A, et al. SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology. 2012 Oct 9; 79(15): 1556-1562.
[73] Han-Xiang Deng et al., Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia Nature 2011 Aug 21;477(7363):211-5. doi: 10.1038/nature10353.
[74] Frisoni GB, Festari C, Massa F et al. European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders Lancet Neurol 2024; 23: 302-312.
[75] Zetterberg H., Van Swieten J.C., Boxer A.L., Rohrer J.D. Review: Fluid biomarkers for frontotemporal dementias. Neuropathol. Appl. Neurobiol. 2019;45:81–87. doi: 10.1111/nan.12530.
[76] Doroszkiewicz J., Groblewska M., Mroczko B. Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases. Int. J. Mol. Sci. 2022;23:4610. doi: 10.3390/ijms23094610.
[77] Teunissen CE, Verberk IMW, Thijssen EH, et al. Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol.2022 Jan; 21(1): 66-77.
[78] Yoshimura T.; Fujita K.; Kawakami S.; Takeda K.; Chan S.; Beligere G.; Dowell B. Stability of Pro-Gastrin-Releasing Peptide inSerum versus Plasma. Tumor Biol. 2008, 29, 224–230.
[79] Bolstad N.; Warren D.J.; Nustad K. Heterophilic antibody interference in immunometric assays. Best Pract. Res. Clin. Endocrinol.Metab. 2013, 27, 647– 661.
[80] Apweiler R.; Aslanidis C.; Deufel T.; Gerstner A.; Hansen J.; Hochstrasser D.; Kellner R.; Kubicek M.; Lottspeich F.;Maser E.; et al. Approaching clinical proteomics: Current state and future fields of application in fluid proteomics. Clin. Chem.Lab. Med. 2009, 47, 724–744.
[81] Agnello L, Gambino CM, Ciaccio AM, Masucci A, Vassallo R, Tamburello M, Scazzone C, Lo Sasso B, Ciaccio M. Biomarcatori molecolari delle malattie neurodegenerative: una guida pratica al loro uso e alla loro interpretazione appropriati nella pratica clinica. Int J Mol Sci. 2024 13 aprile;25(8):4323. doi: 10.3390/ijms25084323.
[82] Foiani M. S. et al. Alla ricerca di nuovi biomarcatori del liquido cerebrospinale della patologia tau nella demenza frontotemporale: una ricerca sfuggente, J Neurol Neurosurg Psichiatria. Luglio 2019;90(7):740-746.doi:10.1136/jnnp- 2018-319266.
[83] Skillbäck T, Farahmand BY, Rosén C, et al. Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia. Brain. 2015 Sep; 138(Pt 9):2716-2731.
[84] Yuan, A.; Veeranna; Sershen, H.; Basavarajappa, B.S.; Smiley, J.F.; Hashim, A.; Bleiwas, C.; Berg, M.; Guifoyle, D.N.;S ubbanna, S.; et al. Neurofilament light interaction with GluN1 modulates neurotransmission and schizophrenia- associatedbehaviors. Transl. Psychiatry 2018, 8, 167.
[85] Khalil, M.; Teunissen, C.E.; Otto, M.; Piehl, F.; Sormani, M.P.; Gattringer, T.; Barro, C.; Kappos, L.; Comabella, M.; Fazekas, F.; et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 2018, 14, 577–589.
[86] Meeter, L.H.H.; Gendron, T.F.; Sias, A.C.; Jiskoot, L.C.; Russo, S.P.; Donker Kaat, L.; Papma, J.M.; Panman, J.L.; van der Ende, E.L.; Dopper, E.G.; et al. Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers. Ann. Clin. Transl. Neurol. 2018,5, 583–597.
[87] De Jong D., Jansen R.W., Pijnenburg Y.A., van Geel W.J., Borm G.F., Kremer H.P., Verbeek M.M. CSF neurofilament proteins in the differential diagnosis of dementia. J. Neurol. Neurosurg. Psychiatry. 2007; 78:936–938. doi: 10.1136/jnnp.2006.107326.
[88] Ducharme S., Dols A., Laforce R., Devenney E., Kumfor F., van den Stock J., Dallaire-Théroux C., Seelaar H., Gossink F., Vijverberg E., et al. Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders. Brain. 2020; 143:1632–1650. doi: 10.1093/brain/awaa018. Erratum in Brain 2020, 143, e62.
[89] Benussi A., Karikari T.K., Ashton N., Gazzina S., Premi E., Benussi L., Ghidoni R., Rodriguez J.L., Emeršič A., Simrén J., et al. Diagnostic and prognostic value of serum NfL and p-Tau181in frontotemporal lobar degeneration. J. Neurol. Neurosurg. Psychiatry. 2020; 91:960–967. doi: 10.1136/jnnp-2020-323487.
[90] Körtvelyessy, P.; Heinze, H.J.; Prudlo, J.; Bittner, D. CSF Biomarkers of Neurodegeneration in Progressive Non-fluent Aphasiaand Other Forms of Frontotemporal Dementia: Clues for Pathomechanisms? Front. Neurol. 2018, 9, 504 .
[91] Wilke, C.; Gillardon, F.; Deuschle, C.; Dubois, E.; Hobert, M.A.; Müller vom Hagen, J.; Krüger, S.; Biskup, S.; Blauwendraat, C.;Hruscha, M.; et al. Serum Levels of Progranulin Do Not Reflect Cerebrospinal Fluid Levels in Neurodegenerative Disease. Curr.Alzheimer Res. 2016, 13, 654–662.
[92] Balendra, R.; Isaacs, A.M. C9orf72-mediated ALS and FTD: Multiple pathways to disease. Nat. Rev. Neurol. 2018, 14, 544–558.
[93] Feneberg, E.; Steinacker, P.; Lehnert, S.; Schneider, A.; Walther, P.; Thal, D.R.; Linsenmeier, M.; Ludolph, A.C.; Otto, M. Limitedrole of free TDP-43 as a diagnostic tool in neurodegenerative diseases. Amyotroph. Lateral Scler. Front. Degener. 2014, 15, 351–356.
[94] Suárez-Calvet, M.; Kleinberger, G.; Araque Caballero, M.; Brendel, M.; Rominger, A.; Alcolea, D.; Fortea, J.; Lleó, A.; Blesa, R.; Gispert, J.D.; et al. sTREM 2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer’sdisease and associate with neuronal injury markers. EMBO Mol. Med. 2016, 8, 466–476.
[95] Tan Y.J.; Siow I.; Saffari S.E.; Ting S.K.S.; Li Z.; Kandiah N.; Tan L.C.S.; Tan E.K.; Ng A.S.L. Plasma Soluble ST2 Levels AreHigher in Neurodegenerative Disorders and Associated with Poorer Cognition. J. Alzheimer’s Dis. 2023, 92, 573–580.
[96] Antonioni A., Emanuela Maria Raho, Piervito Lopriore, Antonia Pia Pace, Raffaela Rita Latino Frontotemporal Dementia, Where Do We Stand? A Narrative Review Int J Mol Sci. 2023 Jul; 24(14): 11732.Published online 2023 Jul21. doi: 10.3390/ijms241411732.
[97] Viswanathan Sowmya , Narayanan Tharangattu N. et al., Biosensori ad effetto di
campo grafene-proteina: rilevamento del glucosio, Materialstoday,Vol. 18, N. 9 ,
Nov. 2015, Pagine 513-522. https://doi.org/10.1016/j.mattod.2015.04.003.
[98] Rogolino A. & Savio G. Tendenze nella microfluiidica, nei micro reattori e nei materiali catalitici prodotti in modo additivo. Material Advances n. 3,2021. Doi: org/10.1039/doma00704H.
[99] Liu W., Zhao L., Blackman B., Parmar M., Wong M.Y., Woo T., Yu F., Chiuchiolo M.J., Sondhi D., Kaminsky S.M., et al. Vectored Intracerebral Immunization with theAnti-Tau Monoclonal Antibody PHF1 Markedly Reduces Tau Pathologyin Mutant Tau Transgenic Mice.J.Neurosci.2016;36:12425–12435.doi: 10.1523/JNEUROSCI.2016-16.2016. Erratum in J.Neurosci. 2017, 37, 3734.
[100] Rhinn H., Tatton N., McCaughey S., Kurnellas M., Rosenthal A. Progranulin as a therapeutic target in neurodegenerative diseases. Trends Pharmacol. Sci. 2022; 43:641–652. doi: 10.1016/j.tips.2021.11.015.
[101] Tran H., Moazami M.P., Yang H., McKenna-Yasek D., Douthwright C.L., Pinto C., Metterville J., Shin M., Sanil N., Dooley C., et al. Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide. Nat. Med. 2022; 28:117–124. doi: 10.1038/s41591-021-01557-6.
[102] Antczak J., Kowalska K., Klimkowicz-Mrowiec A., Wach B., Kasprzyk K., Banach M., Rzeźnicka-Brzegowy K., Kubica J., Słowik A. Repetitive transcranial magnetic stimulation for the treatment of cognitive impairment in frontotemporal dementia: An open-label pilot study. Neuropsychiatr. Dis. Treat. 2018; 14:749–755. doi: 10.2147/NDT.S153213.
[103] Assogna M., Di Lorenzo F., Martorana A., Koch G. Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders. Biomolecules. 2022; 12:1161. doi: 10.3390/biom12081161.
[104] Assogna M., Casula E.P., Borghi I., Bonnì S., Samà D., Motta C., Di Lorenzo F., D’acunto A., Porrazzini F., Minei M., et al. Effects of Palmitoylethanolamide Combined with Luteoline on Frontal Lobe Functions, High Frequency Oscillations, and GABAergic Transmission in Patients with Frontotemporal Dementia. J. Alzheimer’s Dis. 2020; 76:1297–1308. doi: 10.3233/JAD-200426.