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Clinical and Neuroimaging Aspects of Familial Frontotemporal Lobar Degeneration Associated with MAPT and GRN Mutations

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Frontotemporal Dementias

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1281))

Abstract

Numerous kindreds with familial frontotemporal lobar degeneration have been linked to mutations in microtubule-associated protein tau (MAPT) or progranulin (GRN) genes. While there are many similarities in the clinical manifestations and associated neuroimaging findings, there are also distinct differences. In this review, we compare and contrast the demographic/inheritance characteristics, histopathology, pathophysiology, clinical aspects, and key neuroimaging findings between those with MAPT and GRN mutations.

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Abbreviations

ALS:

amyotrophic lateral sclerosis

bvFTD:

behavioral variant frontotemporal dementia

c9FTD/ALS:

frontotemporal dementia and/or amyotrophic lateral sclerosis linked to chromosome 9

C9orf72 :

gene encoding chromosome 9 open reading frame 72

CBS:

corticobasal syndrome

CNS:

central nervous system

FDG-PET:

fluorodeoxyglucose positron emission tomography

FTD:

frontotemporal dementia

FTD/ALS:

frontotemporal dementia with amyotrophic lateral sclerosis

FTLD:

frontotemporal lobar degeneration

GRN :

gene encoding progranulin (or granulin)

MAPT :

gene encoding microtubule-associated protein tau

MRI:

magnetic resonance imaging

PPA:

primary progressive aphasia

References

  1. Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J et al (2009) Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 117(1):15–18

    Article  PubMed  Google Scholar 

  2. Olney NT, Spina S, Miller BL (2017) Frontotemporal Dementia. Neurol Clin 35(2):339–374

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wilhelmsen KC, Lynch T, Pavlou E, Higgins M, Nygaard TG (1994) Localization of disinhibition-dementia-parkinsonism-Amyotrophy complex to 17q21–22. Am J Hum Genet 55:1159–1165

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D’Amato CJ, Gilman S (1997) Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Ann Neurol 41(6):706–715

    Article  CAS  PubMed  Google Scholar 

  5. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H et al (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393(6686):702–705

    Article  CAS  PubMed  Google Scholar 

  6. Rademakers R, Cruts M, Dermaut B, Sleegers K, Rosso SM, Van den Broeck M et al (2002) Tau negative frontal lobe dementia at 17q21: significant finemapping of the candidate region to a 4.8 cM interval. Mol Psychiatry 7(10):1064–1074

    Article  CAS  PubMed  Google Scholar 

  7. Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C et al (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442(7105):916–919

    Article  CAS  PubMed  Google Scholar 

  8. Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D et al (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442(7105):920–924

    Article  CAS  PubMed  Google Scholar 

  9. Moore KM, Nicholas J, Grossman M, McMillan CT, Irwin DJ, Massimo L et al (2020) Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study. Lancet Neurol 19(2):145–156

    Article  CAS  PubMed  Google Scholar 

  10. Olney NT, Ong E, Goh SM, Bajorek L, Dever R, Staffaroni AM et al (2020) Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration. Alzheimers Dement 16(1):49–59

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ramos EM, Dokuru DR, Van Berlo V, Wojta K, Wang Q, Huang AY et al (2020) Genetic screening of a large series of North American sporadic and familial frontotemporal dementia cases. Alzheimers Dement 16(1):118–130

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rosen HJ, Boeve BF, Boxer AL (2020) Tracking disease progression in familial and sporadic frontotemporal lobar degeneration: recent findings from ARTFL and LEFFTDS. Alzheimers Dement 16(1):71–78

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sirkis DW, Geier EG, Bonham LW, Karch CM, Yokoyama JS (2019) Recent advances in the genetics of frontotemporal dementia. Curr Genet Med Rep 7(1):41–52

    Article  PubMed  PubMed Central  Google Scholar 

  14. Che XQ, Zhao QH, Huang Y, Li X, Ren RJ, Chen SD et al (2017) Genetic features of MAPT, GRN, C9orf72 and CHCHD10 gene mutations in Chinese patients with frontotemporal dementia. Curr Alzheimer Res 14(10):1102–1108

    Article  CAS  PubMed  Google Scholar 

  15. Ikeuchi T, Kaneko H, Miyashita A, Nozaki H, Kasuga K, Tsukie T et al (2008) Mutational analysis in early-onset familial dementia in the Japanese population. The role of PSEN1 and MAPT R406W mutations. Dement Geriatr Cogn Disord 26(1):43–49

    Article  CAS  PubMed  Google Scholar 

  16. Kim EJ, Kwon JC, Park KH, Park KW, Lee JH, Choi SH et al (2014) Clinical and genetic analysis of MAPT, GRN, and C9orf72 genes in Korean patients with frontotemporal dementia. Neurobiol Aging 35(5):1213 e13–1213 e17

    Article  CAS  Google Scholar 

  17. Kim HJ, Oh KW, Kwon MJ, Oh SI, Park JS, Kim YE et al (2016) Identification of mutations in Korean patients with amyotrophic lateral sclerosis using multigene panel testing. Neurobiol Aging 37:209 e9–209e16

    Article  CAS  Google Scholar 

  18. Ogaki K, Li Y, Takanashi M, Ishikawa K, Kobayashi T, Nonaka T et al (2013) Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS. Parkinsonism Relat Disord 19(1):15–20

    Article  PubMed  Google Scholar 

  19. Wei Q, Chen X, Chen Y, Ou R, Cao B, Hou Y et al (2019) Unique characteristics of the genetics epidemiology of amyotrophic lateral sclerosis in China. Sci China Life Sci 62(4):517–525

    Article  PubMed  Google Scholar 

  20. Perry DC, Lehmann M, Yokoyama JS, Karydas A, Lee JJ, Coppola G et al (2013) Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 70(6):774–778

    Google Scholar 

  21. Van Deerlin VM, Forman MS, Farmer JM, Grossman M, Joyce S, Crowe A et al (2007) Biochemical and pathological characterization of frontotemporal dementia due to a Leu266Val mutation in microtubule-associated protein tau in an African American individual. Acta Neuropathol 113(4):471–479

    Article  PubMed  CAS  Google Scholar 

  22. Momeni P, DeTucci K, Straub RE, Weinberger DR, Davies P, Grafman J et al (2010) Progranulin (GRN) in two siblings of a Latino family and in other patients with schizophrenia. Neurocase 16(3):273–279

    Article  PubMed  PubMed Central  Google Scholar 

  23. Boeve BF, Tremont-Lukats IW, Waclawik AJ, Murrell JR, Hermann B, Jack CR Jr et al (2005) Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation. Brain 128(Pt 4):752–772

    Article  PubMed  Google Scholar 

  24. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC et al (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367(9):795–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC et al (2014) Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 83(3):253–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Boeve B, Bove J, Brannelly P, Brushaber D, Coppola G, Dever R et al (2020) The longitudinal evaluation of familial frontotemporal dementia subjects protocol: framework and methodology. Alzheimers Dement 16(1):22–36

    Article  PubMed  PubMed Central  Google Scholar 

  27. Boxer AL, Gold M, Feldman H, Boeve BF, Dickinson SL, Fillit H et al (2020) New directions in clinical trials for frontotemporal lobar degeneration: methods and outcome measures. Alzheimers Dement 16(1):131–143

    Article  PubMed  PubMed Central  Google Scholar 

  28. Irwin DJ (2016) Tauopathies as clinicopathological entities. Parkinsonism Relat Disord 22(Suppl 1):S29–S33

    Article  PubMed  Google Scholar 

  29. Bodea LG, Eckert A, Ittner LM, Piguet O, Gotz J (2016) Tau physiology and pathomechanisms in frontotemporal lobar degeneration. J Neurochem 138(Suppl 1):71–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17(1):5–21

    Article  CAS  PubMed  Google Scholar 

  31. Karch CM, Kao AW, Karydas A, Onanuga K, Martinez R, Argouarch A et al (2019) A comprehensive resource for induced pluripotent stem cells from patients with primary Tauopathies. Stem Cell Reports 13(5):939–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Vaquer-Alicea J, Diamond MI (2019) Propagation of protein aggregation in neurodegenerative diseases. Annu Rev Biochem 88:785–810

    Article  CAS  PubMed  Google Scholar 

  33. Mackenzie IR, Neumann M (2016) Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. J Neurochem 138(Suppl 1):54–70

    Article  CAS  PubMed  Google Scholar 

  34. Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol 114(1):5–22

    Article  PubMed  PubMed Central  Google Scholar 

  35. Galimberti D, Fenoglio C, Scarpini E (2018) Progranulin as a therapeutic target for dementia. Expert Opin Ther Targets 22(7):579–585

    Article  CAS  PubMed  Google Scholar 

  36. Bateman A, Cheung ST, Bennett HPJ (2018) A brief overview of progranulin in health and disease. Methods Mol Biol 1806:3–15

    Article  CAS  PubMed  Google Scholar 

  37. Kao AW, McKay A, Singh PP, Brunet A, Huang EJ (2017) Progranulin, lysosomal regulation and neurodegenerative disease. Nat Rev Neurosci 18(6):325–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S et al (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51(6):1546–1554

    Article  CAS  PubMed  Google Scholar 

  39. Rascovsky K, Hodges JR, Kipps CM, Johnson JK, Seeley WW, Mendez MF et al (2007) Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions. Alzheimer Dis Assoc Disord 21(4):S14–S18

    Article  PubMed  Google Scholar 

  40. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134(Pt 9):2456–2477

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rosen HJ, Gorno-Tempini ML, Goldman WP, Perry RJ, Schuff N, Weiner M et al (2002) Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 58(2):198–208

    Article  CAS  PubMed  Google Scholar 

  42. Heuer HW, Wang P, Rascovsky K, Wolf A, Appleby B, Bove J et al (2020) Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort. Alzheimers Dement 16(1):60–70

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rohrer JD, Nicholas JM, Cash DM, van Swieten J, Dopper E, Jiskoot L et al (2015) Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the genetic frontotemporal dementia initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol 14(3):253–262

    Article  PubMed  PubMed Central  Google Scholar 

  44. Whitwell JL, Jack CR Jr, Parisi JE, Knopman DS, Boeve BF, Petersen RC et al (2011) Imaging signatures of molecular pathology in behavioral variant frontotemporal dementia. J Mol Neurosci 45(3):372–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Whitwell JL, Weigand SD, Boeve BF, Senjem ML, Gunter JL, DeJesus-Hernandez M et al (2012) Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 135(Pt 3):794–806

    Article  PubMed  PubMed Central  Google Scholar 

  46. Whitwell JL, Boeve BF, Weigand SD, Senjem ML, Gunter JL, Baker MC et al (2015) Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images. Eur J Neurol 22(5):745–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF et al (2011) Classification of primary progressive aphasia and its variants. Neurology 76(11):1006–1014

    Article  PubMed  PubMed Central  Google Scholar 

  48. Snowden JS, Pickering-Brown SM, Mackenzie IR, Richardson AM, Varma A, Neary D et al (2006) Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia. Brain 129:3091–3102

    Article  CAS  PubMed  Google Scholar 

  49. Whitwell JL, Jack CR Jr, Boeve BF, Senjem ML, Baker M, Ivnik RJ et al (2009) Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations. Neurology 73(13):1058–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Beck J, Rohrer JD, Campbell T, Isaacs A, Morrison KE, Goodall EF et al (2008) A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series. Brain 131(Pt 3):706–720

    Article  PubMed  Google Scholar 

  51. Kelley BJ, Haidar W, Boeve BF, Baker M, Graff-Radford NR, Krefft T et al (2009) Prominent phenotypic variability associated with mutations in progranulin. Neurobiol Aging 30(5):739–751

    Article  CAS  PubMed  Google Scholar 

  52. Ygland E, van Westen D, Englund E, Rademakers R, Wszolek ZK, Nilsson K et al (2018) Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review. Alzheimers Res Ther 10(1):2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Caroppo P, Belin C, Grabli D, Maillet D, De Septenville A, Migliaccio R et al (2015) Posterior cortical atrophy as an extreme phenotype of GRN mutations. JAMA Neurol 72(2):224–228

    Article  PubMed  Google Scholar 

  54. Crutch SJ, Schott JM, Rabinovici GD, Boeve BF, Cappa SF, Dickerson BC et al (2013) Shining a light on posterior cortical atrophy. Alzheimers Dement 9(4):463–465

    Google Scholar 

  55. Wolk DA, Price JC, Madeira C, Saxton JA, Snitz BE, Lopez OL et al (2012) Amyloid imaging in dementias with atypical presentation. Alzheimers Dement 8(5):389–398

    Article  PubMed  PubMed Central  Google Scholar 

  56. Boeve BF, Lang AE, Litvan I (2003) Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol 54(Suppl 5):S15–S19

    Article  PubMed  Google Scholar 

  57. Lee SE, Rabinovici GD, Mayo MC, Wilson SM, Seeley WW, DeArmond SJ et al (2011) Clinicopathological correlations in corticobasal degeneration. Ann Neurol 70(2):327–340

    Article  PubMed  PubMed Central  Google Scholar 

  58. Boeve BF, Graff-Radford NR (2012) Cognitive and behavioral features of c9FTD/ALS. Alzheimers Res Ther 4(4):29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Snowden JS, Rollinson S, Thompson JC, Harris JM, Stopford CL, Richardson AM et al (2012) Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain 135(Pt 3):693–708

    Article  PubMed  PubMed Central  Google Scholar 

  60. Khan BK, Woolley JD, Chao S, See T, Karydas AM, Miller BL et al (2012) Schizophrenia or neurodegenerative disease prodrome? Outcome of a first psychotic episode in a 35-year-old woman. Psychosomatics 53(3):280–284

    Article  PubMed  PubMed Central  Google Scholar 

  61. Block NR, Sha SJ, Karydas AM, Fong JC, De May MG, Miller BL et al (2016) Frontotemporal dementia and psychiatric illness: emerging clinical and biological links in gene carriers. Am J Geriatr Psychiatry 24(2):107–116

    Article  PubMed  Google Scholar 

  62. Warren JD, Rohrer JD, Rossor MN (2013) Clinical review. Frontotemporal dementia. BMJ 347:f4827

    Article  PubMed  PubMed Central  Google Scholar 

  63. Bang J, Spina S, Miller BL (2015) Frontotemporal dementia. Lancet 386(10004):1672–1682

    Article  PubMed  PubMed Central  Google Scholar 

  64. Wszolek ZK, Pfeiffer RF (1992) Genetic considerations in movement disorders. Curr Opin Neurol Neurosurg 5(3):324–330

    CAS  PubMed  Google Scholar 

  65. Wszolek ZK, Kardon RH, Wolters EC, Pfeiffer RF (2001) Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17): PPND family. A longitudinal videotape demonstration. Mov Disord 16(4):756–760

    Article  CAS  PubMed  Google Scholar 

  66. Rossi G, Marelli C, Farina L, Laura M, Maria Basile A, Ciano C et al (2008) The G389R mutation in the MAPT gene presenting as sporadic corticobasal syndrome. Mov Disord 23(6):892–895

    Article  PubMed  Google Scholar 

  67. Nicholson AM, Rademakers R (2016) What we know about TMEM106B in neurodegeneration. Acta Neuropathol 132(5):639–651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pottier C, Zhou X, Perkerson RB 3rd, Baker M, Jenkins GD, Serie DJ et al (2018) Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17(6):548–558

    Article  PubMed  PubMed Central  Google Scholar 

  69. Whitwell JL, Weigand SD, Gunter JL, Boeve BF, Rademakers R, Baker M et al (2011) Trajectories of brain and hippocampal atrophy in FTD with mutations in MAPT or GRN. Neurology 77(4):393–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Frank AR, Wszolek ZK, Jack CR Jr, Boeve BF (2007) Distinctive MRI findings in pallidopontonigral degeneration (PPND). Neurology 68(8):620–621

    Article  PubMed  Google Scholar 

  71. Jacova C, Hsiung GY, Tawankanjanachot I, Dinelle K, McCormick S, Gonzalez M et al (2013) Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology 81(15):1322–1331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. McDade E, Boeve BF, Burrus TM, Boot BP, Kantarci K, Fields J et al (2012) Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin. Neurology 78(16):1245–1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chen Q, Boeve BF, Tosakulwong N, Lesnick T, Brushaber D, Dheel C et al (2019) Brain MR spectroscopy changes precede frontotemporal lobar degeneration Phenoconversion in Mapt mutation carriers. J Neuroimaging 29(5):624–629

    Article  PubMed  PubMed Central  Google Scholar 

  74. Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick TG, Brushaber D et al (2019) Rates of lobar atrophy in asymptomatic MAPT mutation carriers. Alzheimers Dement (N Y) 5:338–346

    Article  Google Scholar 

  75. Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick T, Brushaber D et al (2019) Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study. Neurobiol Aging

    Google Scholar 

  76. Chen Q, Boeve BF, Schwarz CG, Reid R, Tosakulwong N, Lesnick TG et al (2019) Tracking white matter degeneration in asymptomatic and symptomatic MAPT mutation carriers. Neurobiol Aging 83:54–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Jiskoot LC, Panman JL, Meeter LH, Dopper EGP, Donker Kaat L, Franzen S et al (2019) Longitudinal multimodal MRI as prognostic and diagnostic biomarker in presymptomatic familial frontotemporal dementia. Brain 142(1):193–208

    Article  PubMed  Google Scholar 

  78. Sudre CH, Bocchetta M, Cash D, Thomas DL, Woollacott I, Dick KM et al (2017) White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort. NeuroImage: Clinical 15:171–180

    Article  Google Scholar 

  79. Tavares TP, Mitchell DGV, Coleman K, Shoesmith C, Bartha R, Cash DM et al (2019) Ventricular volume expansion in presymptomatic genetic frontotemporal dementia. Neurology 93(18):e1699–ee706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Choi Y, Ha S, Lee YS, Kim YK, Lee DS, Kim DJ (2018) Development of tau PET imaging ligands and their utility in preclinical and clinical studies. Nucl Med Mol Imaging 52(1):24–30

    Article  CAS  PubMed  Google Scholar 

  81. Ikeda A, Shimada H, Nishioka K, Takanashi M, Hayashida A, Li Y et al (2019) Clinical heterogeneity of frontotemporal dementia and parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features. Mov Disord 34(4):568–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tsai RM, Bejanin A, Lesman-Segev O, LaJoie R, Visani A, Bourakova V et al (2019) (18)F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. Alzheimers Res Ther 11(1):13

    Article  PubMed  PubMed Central  Google Scholar 

  83. Schofield EC, Halliday GM, Kwok J, Loy C, Double KL, Hodges JR (2010) Low serum progranulin predicts the presence of mutations: a prospective study. J Alzheimers Dis 22(3):981–984

    Article  CAS  PubMed  Google Scholar 

  84. Guven G, Bilgic B, Tufekcioglu Z, Erginel Unaltuna N, Hanagasi H, Gurvit H et al (2019) Peripheral GRN mRNA and serum progranulin levels as a potential indicator for both the presence of splice site mutations and individuals at risk for frontotemporal dementia. J Alzheimers Dis 67(1):159–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Galimberti D, Fumagalli GG, Fenoglio C, Cioffi SMG, Arighi A, Serpente M et al (2018) Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study. Neurobiol Aging 62:245 e9–245e12

    Article  CAS  Google Scholar 

  86. Zhao Y, Xin Y, Meng S, He Z, Hu W (2019) Neurofilament light chain protein in neurodegenerative dementia: a systematic review and network meta-analysis. Neurosci Biobehav Rev 102:123–138

    Article  CAS  PubMed  Google Scholar 

  87. Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A et al (2016) Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology 87(13):1329–1336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ljubenkov PA, Staffaroni AM, Rojas JC, Allen IE, Wang P, Heuer H et al (2018) Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory. Ann Clin Transl Neurol 5(10):1250–1263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Meeter LH, Dopper EG, Jiskoot LC, Sanchez-Valle R, Graff C, Benussi L et al (2016) Neurofilament light chain: a biomarker for genetic frontotemporal dementia. Ann Clin Transl Neurol 3(8):623–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. van der Ende EL, Meeter LH, Poos JM, Panman JL, Jiskoot LC, Dopper EGP et al (2019) Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study. Lancet Neurol 18(12):1103–1111

    Article  PubMed  Google Scholar 

  91. Heller C, Foiani MS, Moore K, Convery R, Bocchetta M, Neason M et al (2020) Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. J Neurol Neurosurg Psychiatry 91(3):263–270

    Article  PubMed  Google Scholar 

  92. Ljubenkov PA, Miller Z, Mumford P, Zhang J, Allen IE, Mitic L et al (2019) Peripheral innate immune activation correlates with disease severity in GRN Haploinsufficiency. Front Neurol 10:1004

    Article  PubMed  PubMed Central  Google Scholar 

  93. Staffaroni AM, Cobigo Y, Goh SM, Kornak J, Bajorek L, Chiang K et al (2020) Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration. Alzheimers Dement 16(1):37–48

    Article  PubMed  PubMed Central  Google Scholar 

  94. Chen Q, Boeve BF, Tosakulwong N, Lesnick T, Brushaber D, Dheel C et al (2019) Frontal lobe (1)H MR spectroscopy in asymptomatic and symptomatic MAPT mutation carriers. Neurology 93(8):e758–e765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Cohn-Hokke PE, Elting MW, Pijnenburg YA, van Swieten JC (2012) Genetics of dementia: update and guidelines for the clinician. Am J Med Genet B Neuropsychiatr Genet 159B(6):628–643

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by NIH grants AG045390, NS092089, AG062677, AG063911, AG016574, AG019724, AG062422, AG056749, and AG045333.

We thank our many collaborators across the ALLFTD, GENFI, DINAD, and FPI consortia. The images in the Figure are courtesy of Drs. Val Lowe, Clifford Jack Jr., and Kejal Kantarci. We particularly thank the patients and their families for participating in aging and neurodegenerative disease research.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Bradley F. Boeve

  2. Department of Neurology, University of California San Francisco, San Francisco, CA, USA

    Howard Rosen

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  1. Bradley F. Boeve
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Correspondence to Bradley F. Boeve .

Editor information

Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA

    Bernardino Ghetti

  2. International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

    Emanuele Buratti

  3. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Bradley Boeve

  4. VIB Center for Molecular Neurology University of Antwerp-CDE Antwerpen, Belgium, Department of Neuroscience Mayo Clinic Jacksonville, FL, USA, Antwerpen, Belgium

    Rosa Rademakers

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Boeve, B.F., Rosen, H. (2021). Clinical and Neuroimaging Aspects of Familial Frontotemporal Lobar Degeneration Associated with MAPT and GRN Mutations. In: Ghetti, B., Buratti, E., Boeve, B., Rademakers, R. (eds) Frontotemporal Dementias . Advances in Experimental Medicine and Biology, vol 1281. Springer, Cham. https://doi.org/10.1007/978-3-030-51140-1_6

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