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Chapter 18 - Pharmacologictherapy for FTD and related disorders

Current options and future strategies

from Section 5 - Treatment

Published online by Cambridge University Press:  05 May 2016

Bradford C. Dickerson
Affiliation:
Department of Neurology, Massachusetts General Hospital
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Publisher: Cambridge University Press
Print publication year: 2016

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References

Kaye, ED, Petrovic-Poljak, A, Verhoeff, NP, Freedman, M. Frontotemporal dementia and pharmacologic interventions. J Neuropsychiatry Clin Neurosci 2010;22 (1):1929.Google Scholar
Angoa-Perez, M, Kane, MJ, Briggs, DI, Sykes, CE, Shah, MM, Francescutti, DM, et al. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity. J Neurochem 2012;121:974–84.Google Scholar
Procter, AW, Qurne, M, Francis, PT. Neurochemical features of frontotemporal dementia. Dement Geriatr Cogn Disord 1999;10 Suppl 1:80–4.Google Scholar
Franceschi, M, Anchisi, D, Pelati, O, Zuffi, M, Matarrese, M, Moresco, RM, et al. Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration. Ann Neurol 2005;57:216–25.CrossRefGoogle ScholarPubMed
Yang, Y, Schmitt, HP. Frontotemporal dementia: evidence for impairment of ascending serotoninergic but not noradrenergic innervations. Immunocytochemical and quantitative study using a graph method. Acta Neuropathol 2001;101:256–70.Google Scholar
Hermann, N, Black, SE, Chow, T, Cappell, J, Tang-Wai, DF, Lanctôt, KL. Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatry 2012;20:789–97.Google Scholar
Swartz, JR, Miller, BL, Lesser, IM, Darby, AL. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry 1997;58:212–16.CrossRefGoogle ScholarPubMed
Chow, TW, Mendez, MF. Goals in symptomatic pharmacologic management of frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen 2002;17:276–72.Google Scholar
Moretti, R, Torre, P, Antonello, RM, Cazzato, G, Bava, A. Frontotemporal dementia: paroxetine as a possible treatment of behavioral symptoms. A randomized, controlled, open 14-month study. Eur Neurol 2003;49:1319.CrossRefGoogle ScholarPubMed
Mendez, MF, Shapira, JS, Miller, BL. Stereotypical movements and frontotemporal dementia. Mov Disord 2005;20:742–5.Google Scholar
Anneser, JM, Jox, RJ, Borasio, GD. Inappropriate sexual behavior in a case of ALS and FTD: successful treatment with sertraline. Amyotroph Lateral Scler 2007;8:189–90.Google Scholar
Prodan, CI, Monnon, M, Ross, ED. Behavioral abnormalities associated with rapid deterioration of language functions in semantic dementia respond to sertraline. J Neurol Neurosurg Psychiatry 2009;80:1416–17.Google Scholar
Ikeda, M, Shigenobu, K, Fukuhara, R, Hokoishi, K, Maki, N, Nebu, A, et al. Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients. Dement Geriatr Cogn Disord 2004;17:117–21.Google Scholar
Furlan, JC, Henri-Bhargava, A, Freedman, M. Clomipramine in the treatment of compulsive behavior in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord 2014;28:95–8.Google Scholar
Deakin, JB, Rahman, S, Nestor, PJ, Hodges, JR, Sahakian, BJ. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharamcology(Berl) 2004;172:400–8.Google Scholar
Lebert, F, Stekke, W, Hasenbroekx, C, Pasquier, F. Frontotemoporal dementia: a randomized, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004;17:355–9.Google Scholar
Huey, ED, Putnam, KT, Grafman, J. A systematic review of neurotransmitter deficits and treatments. Neurology 2006;66:1722.Google Scholar
Moretti, R, Torre, P, Antonello, RM, Cattaruzza, T, Cazzato, G, Bava, A. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging 2004;21:93–107.Google Scholar
Kertesz, A, Morlog, D, Light, M, Blair, M, Davidson, W, Jesso, S, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord 2008;25:178–85.Google Scholar
Mendez, MF, Shapira, JS, McMurtray, A, Licht, E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry 2007;15:84–7.Google Scholar
Kimura, T, Takamatsu, J. Pilot study of pharmacological treatment for frontotemporal dementia: risk of donepezil treatment for behavioral and psychological symptoms. Geriatr Gerontol Int 2013;13:506–7.Google Scholar
Rinne, JO, Laine, M, Kaasinen, V, Norvasuo-Heilä, MK, Någren, K, Helenius, H. Striatal dopamine transporter and extrapyramidal symptoms in frontotemporal dementia. Neurology 2002;58:1489–93.CrossRefGoogle ScholarPubMed
Sperfeld, AD, Collatz, MB, Baier, H, Palmbach, M, Storch, A, Schwarz, J, et al. FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann Neurol 1999;46:708–15.Google Scholar
Kanazawa, I, Kwak, S, Sasaki, H, Muramoto, O, Mizutani, T, Hori, A, et al. Studies on neurotransmitter markers of the basal ganglia in Pick's disease, with special reference to dopamine reduction. J Neurol Sci 1988;83:6374.Google Scholar
Curtis, RC, Resch, DS. Case of Pick's central lobar atrophy with apparent stabilization of cognitive decline after treatment with risperidone. J Clin Psychopharmacol 2000;20:384–5.Google Scholar
Fellgiebel, A, Müller, MJ, Hiemke, C, Bartenstein, P, Schreckenberger, M. Clinical improvement in a case of frontotemporal dementia under aripiprazole treatment corresponds to partial recovery of disturbed frontal glucose metabolism. World J Biol Psychiatry 2007;8:123–6.Google Scholar
Reeves, RR, Perry, CL. Aripiprazole for sexually inappropriate vocalizations in frontotemporal dementia. J Clin Psychopharmacol 2013;33:145–6.Google Scholar
Moretti, R, Torre, P, Antonello, RM, Cazzato, G, Griggio, S, Bava, A. Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer's disease and other dementias: a 24-month follow-up of 68 patients. Am J Alzheimers Dis Other Demen 2003;18:205–14.CrossRefGoogle ScholarPubMed
Huey, ED, Garcia, C, Wassermann, EM, Tierney, MC, Grafman, J. Stimulant treatment of frontotemporal dementia in 8 patients. J Clin Psychiatry 2008;69:1981–2.Google Scholar
Pijnenburg, YA, Sampson, EL, Harvey, RJ, Fox, NC, Rossor, MN. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry 2003;18:6772.Google Scholar
Moretti, R, Torre, P, Antonello, RM, Cazzato, G, Bava, A. Effects of selegiline on fronto-temporal dementia: a neuropsychological evaluation. Int J Geriatr Psychiatry 2002;17:391–2.Google Scholar
Rahman, S, Robbins, TW, Hodges, JR, Mehta, MA, Nestor, PJ, Clark, L, et al. Methylphenidate (‘Ritalin’) can ameliorate abnormal risk-taking behavior in the frontal variant of frontotemporal dementia. Neuropsychopharmacology 2006;31:651–8.Google Scholar
Reed, DA, Johnson, NA, Thompson, C, Weintraub, S, Mesulam, MM. A clinical trial of bromocriptine for treatment of primary progressive aphasia. Ann Neurol 2004;56:750.Google Scholar
Poetter, CE, Stewart, JT. Treatment of indiscriminate, inappropriate sexual behavior in frontotemporal dementia with carbamazepine. J Clin Psychopharmacol 2012;31:137–8.Google Scholar
Cruz, M, Marinho, V, Fontenelle, LF, Engelhardt, E, Laks, J. Topiramate may modulate alcohol abuse but not other compulsive behaviors in frontotemporal dementia: case report. Cogn Behav Neurol 2008;21:104–6.Google Scholar
Nestor, PJ. Reversal of abnormal eating and drinking behavior in a frontotemporal lobar degeneration patient using low-dose topiramate. J Neurol Neurosurg Psychiatry 2012;83:349–50.CrossRefGoogle Scholar
Singam, C, Walterfang, M, Mocellin, R, Evans, A, Velakoulis, D. Topiramate for abnormal eating behavior in frontotemporal dementia. Behav Neurol 2013;27:285–6.Google Scholar
Shinagawa, S, Tsuno, N, Nakayama, K. Managing abnormal eating behaviors in frontotemporal lobar degeneration in patients with topiramate. Psychogeriatrics 2013;13:5861.Google Scholar
Reisberg, B, Doody, R, Stöffler, A, Schmitt, F, Ferris, S, Möbius, HJ; Memantine Study Group. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003;348:1333–41.Google Scholar
Tariot, PN, Farlow, MR, Grossberg, GT, Graham, SM, McDonald, S, Geergel, I, et al. Memantine treatment in patients with moderate to severe Alzheimer Disease already receiving donepezil. JAMA 2004;291:317–24.CrossRefGoogle ScholarPubMed
Diehl-Schmid, J, Förstl, H, Perneczky, R, Pohl, C, Kurz, A. A 6-month, open-label study of memantine in patients with frontotemporal dementia. Int J Geriatr Psychiatry 2008;23:754–9.Google Scholar
Cummings, JL, Schneider, E, Tariot, PN, Graham, SM; Memantine MEM-MD-02 Study Group. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil. Neurology 2006;67:5763.Google Scholar
Swanberg, MM. Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord 2007;21:164–6.Google Scholar
Boxer, AL, Lipton, AM, Womack, K, Merrilees, J, Neuhaus, J, Pavlic, D, et al. An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord 2009;23:211–17.Google Scholar
Vercelletto, M, Boutoleau-Bretonnière, C, Volteau, C, Puel, M, Auriacombe, S, Sarazin, M, et al. Memantine in behavioral variant frontotemporal dementia: negative results. J Alzheimer Dis 2011;23:749–59.Google Scholar
Boxer, AL, Knopman, DS, Kaufer, DI, Grossman, M, Onyike, C, Graf-Radford, N, et al. Memantine in patients with frontotemporal lobar degeneration: a multicenter, randomized, double-blind, placebo-controlled trial. Lancet Neurol 2013;12:149–56.Google Scholar
Khlistunova, I, Biernat, J, Wang, Y, Pickhardt, M, von Bergen, M, Gazova, Z, et al. Inducible expression of tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J Biol Chem 2006;281:1205–14.Google Scholar
Van der Jeugd, A, Hochgräfe, K, Ahmed, T, Decker, JM, Sydow, A, Hofmann, A, et al. Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human tau. Acta Neuropathol 2012;123:787805.Google Scholar
Bramblett, GT, Goedert, M, Jakes, R, Merrick, SE, Trojanowski, JQ, Lee, VM. Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron 1993;10: 1089–99.Google Scholar
Hampel, H, Ewers, M, Bürger, K, Annas, P, Mörtberg, A, Bogstedt, A, et al. Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry 2009;70: 922–31.Google Scholar
Tolosa, E, Litvan, I, Höglinger, GU, Burn, D, Lees, A, Andrés, MV, et al. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord 2014;29:470–8. Feb 14. doi: 10.1002/mds.25824. [Epub ahead of print]Google Scholar
Min, SW, Cho, SH, Zhou, Y, Schroeder, S, Haroutunian, V, Seeley, WW, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 2010;67:853–66.Google Scholar
Boxer, AL, Gold, M, Huey, E, Gao, FB, Burton, EA, Chow, T, et al. Frontotemporal degeneration, the next therapeutic frontier: molecules and animal models for frontotemporal degeneration drug development. Alzheimers Dement 2013;9:176–88.Google Scholar
Boimel, M, Grigoriadis, N, Lourbopoulos, A, Haber, E, Abramsky, O, Rosenmann, H. Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice. Exp Neurol 2010;224:472–85.Google Scholar
Asuni, AA, Boutajangout, A, Quartermain, D, Sigurdsson, EM. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci 2007;27:9115–29.Google Scholar
Boutajangout, A, Quartermain, D, Sigurdsson, EM. Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 2010;30:16559–66.Google Scholar
Fierce Biotech [internet][place unknown][publisher unknown][Jan 2014] Available from http://www.fiercevaccines.com/story/ac-immune-begins-first-trial-tau-targeting-alzheimers-vaccine/2014-01-13Google Scholar
Boutajangout, A, Ingadottir, J, Davies, P, Sigurdsson, EM. Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J Neurochem 2011;118:658–67.Google Scholar
Chai, X, Wu, S, Murray, TK, Kinley, R, Cella, CV, Sims, H, et al. Passive immunization with anti-tau antibodies in two transgenic models: reduction of tau pathology and delay of disease progression. J Biol Chem 2011;286:34457–67.Google Scholar
Yanamandra, K, Kfoury, N, Jiang, H, Mahan, TE, Ma, S, Maloney, SE, et al. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 2013;80:402–14.Google Scholar
Higuchi, M, Lee, VM, Trojanowski, JQ. Tau and axonopathy in neurodegenerative disorders. Neuromolecular Med 2002;2:131–50.Google Scholar
Erez, H, Shemesh, OA, Spira, ME. Rescue of tau-induced synaptic transmission pathology by paclitaxel. Front Cell Neurosci 2014;8:34. doi: 10.3389/fncel.2014.00034CrossRefGoogle ScholarPubMed
Brunden, KR, Ballatore, C, Lee, VM, Smith, AB 3rd, Trojanowski, JQ. Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies. Biochem Soc Trans 2012;40:661–6.Google Scholar
Barten, DM, Fanara, P, Andorfer, C, Hoque, N, Wong, PY, Husted, KH, et al. Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027. J Neurosci 2012;32:7137–45.Google Scholar
ClinicalTrials.gov [internet][place unknown][NIH][Oct 2013] http://clinicaltrials.gov/ct2/show/NCT01966666?term-tpi+287&rankGoogle Scholar
MacKenzie, IR, Neumann, M, Bigio, EH, Cairns, NJ, Alafuzoff, I, Kril, J, et al. Nomenclature for neuropathological subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 2009;117:1518.Google Scholar
Sephton, CF, Cenik, B, Cenik, BK, Herz, J, Yu, G. TDP-43 in central nervous system development and function: clues to TDP-43 associated neurodegeneration. Biol Chem 2012;393:589–94.Google Scholar
Arnold, ES, Ling, SC, Huelga, SC, Lagier-Tourenne, C, Polymenidou, M, Ditsworth, D, et al. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci USA 2013;110:E736–45.Google Scholar
Janssens, J, Wils, H, Kleinberger, G, Joris, G, Cuijt, I, Ceuterick-de Groote, C, et al. Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice. Mol Neurobiol 2013;48:2235.Google Scholar
Huang, C, Tong, J, Bi, F, Zhou, H, Xia, XG. Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats. J. Clin Invest 2012;122:107–18.Google Scholar
Hu, WT, Watts, K, Grossman, M, Glass, J, Lah, JJ, Hales, C, et al. Reduced CSF p-tau181 to tau ratio is a biomarker for FTLD-TDP. Neurology 2013;81:1945–52.Google Scholar
Maruyama, M, Shimada, H, Suhara, T, Shinotoh, H, Ji, B, Maeda, J, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 2013;79(6):1094–108.Google Scholar
van Swieten, JC, Heutink, P. Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia. Lancet Neurol 2008;7:965–74.Google Scholar
Finch, N, Baker, M, Crook, R, Swanson, K, Kuntz, K, Surtees, R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 2009;132:583–91.Google Scholar
Ghidoni, R, Benussi, L, Glionna, M, Franzoni, M, Binetti, G. Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology 2008;71:1235–39.Google Scholar
Sleegers, K, Brouwers, N, Van Damme, P, Engelborghs, S, Gijselinck, I, van der Zee, J, et al. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol 2009;65:603–9.Google Scholar
Rademakers, R, Eriksen, JL, Baker, M, Robinson, T, Ahmed, Z, Lincoln, SJ, et al. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet 2008;17:3631–42.CrossRefGoogle Scholar
Tang, W, Lu, Y, Tian, QY, Zhang, Y, Guo, FJ, Liu, GY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 2011;332:478–84.Google Scholar
Miller, ZA, Rankin, KP, Graff-Radford, NR, Takada, LT, Sturm, VE, Cleveland, CM, et al. TDP-43 frontotemporal lobar degeneration and autoimmune disease. J Neurol Neurosurg Psychiatry 2013;84:956–62.Google Scholar
Thurner, L, Preuss, KD, Fadle, N, Regitz, E, Klemm, P, Zaks, M, et al. Progranulin antibodies in autoimmune disease. J Autoimmun 2013;42:2938.Google Scholar
Cenik, B, Sephton, CF, Dewey, CM, Xian, X, Wei, S, Yu, K, et al. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J Biol Chem 2011;286:16101–8.Google Scholar
Lee, WC, Almeida, S, Prudencio, M, Caulfield, TR, Zhang, YJ, Bauer, PO, et al. Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency. Hum Mol Genet 2014;23(6):1467–78. doi: 10.1093/hmg/ddt534. [Epub 2013]Google Scholar
Capell, A, Liebscher, S, Fellerer, K, Brouwers, N, Willem, M, Lammich, S, et al. Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase. J Neurosci 2011;31:1885–94.Google Scholar
Alberici, A, Archetti, S, Pilotto, A, Premi, E, Cosseddu, M, Bianchetti, A, et al. Results from a pilot study on amiodarone administration in monogenic frontotemporal dementia with granulin mutation. Neurol Sci 2014;35(8):1215–19.Google Scholar
Sjögren, M, Folkesson, S, Blennow, K, Tarkowski, E. Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications. J Neurol Neurosurg Psychiatry 2004;75:1574–6.Google Scholar
Perry, DC, Lehmann, M, Yokoyama, JS, Karydas, A, Lee, JJ, Coppola, G, et al. Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 2013;70:77477–8.Google Scholar
Sha, SJ, Boxer, A. Treatment implications of C9ORF72. Alzheimers Res Ther 2012;4:46.Google Scholar
Boxer, AL, Mackenzie, IR, Boeve, BF, Baker, M, Seeley, WW, Crook, R, et al. Clinical, neuroimaging and neuropatholgoical features of a new chromosome 9p-linked FTD-ALS family. J Neurol Neurosurg Psychiatry 2011;82:196203.Google Scholar
DeJesus-Hernandez, M, Mackenzie, IR, Boeve, BF, Boxer, AL, Baker, M, Rutherford, NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011;72:24556.Google Scholar
Renton, AE, Majounie, E, Waite, A, Simón-Sánchez, J, Rollinson, S, Gibbs, JR, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011;72:257–68.Google Scholar
Al-Sarraj, S, King, A, Troakes, C, Smith, B, Maekawa, S, Bodi, I, et al. p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS. Acta Neuropathol 2011;122:691702.Google Scholar
Levine, TP, Daniels, RD, Gatta, AT, Wong, LH, Hayes, MJ. The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs. Bioinformatics 2013;29:499503.Google Scholar
Ashe, PE, Bieniek, KF, Gendron, TF, Caulfield, T, Lin, WL, DeJesus-Hernandez, M, et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 2013;77 (4):639–46.Google Scholar
Miller, T, Pestronk, A, David, W, Rothstein, J, Simpson, E, Appel, SH, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomized, first-in-man study. Lancet Neurol 2013;12:435–42.Google Scholar
Donnelly, CJ, Zhang, PW, Pham, JT, Heusler, AR, Mistry, NA, Vidensky, S, et al. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 2013;80:415–28.Google Scholar
Lagier-Tourenne, C, Baughn, M, Rigo, F, Sun, S, Liu, P, Li, HR, et al. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci USA 2013;110:E4530–9.Google Scholar
Flannick, J, Thorleifsson, G, Beer, NL, Jacobs, SB, Grarup, N, Burtt, NP, et al. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet 2014;46(4):357–63. doi: 10.1038/ng.2915.Google Scholar
Takahashi, K, Tanabe, K, Ohnuki, M, Narita, M, Ichisaka, T, Tomoda, K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–72.Google Scholar
Almeida, S, Gascon, E, Tran, H, Chou, HJ, Gendron, TF, Degroot, S, et al. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC derived-human neurons. Acta Neuropathol 2013;126:385–99.Google Scholar
Almeida, S, Zhang, Z, Coppola, G, Mao, W, Futai, K, Karydas, A, et al. Induced pluripotent stem cell models of progranulin-deficient frontotemporal dementia uncover specific reversible neuronal defects. Cell Rep 2012;2:789–98.Google Scholar
Fong, H, Wang, C, Knoferle, J, Walker, D, Balestra, ME, Tong, LM, et al. Genetic correction of tauopathy phenotypes in neurons derived from human induced pluripotent stem cells. Stem Cell Reports 2013;1:226–34.Google Scholar
Alzforum [internet][publisher unknown][date unknown] Available from http://www.alzforum.org/research-modelsGoogle Scholar
Santacruz, K, Lewis, J, Spires, T, Paulson, J, Kotilinek, L, Ingelsson, M, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005;309:476–81.Google Scholar
Tsai, KJ, Yang, CH, Fang, YH, Cho, KH, Chien, WL, Wang, WT, et al. Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. J Exp Med 2010;207:1661–73.Google Scholar
Yin, F, Dumont, M, Banerjee, R, Ma, Y, Li, H, Lin, MT, et al. Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia. FASEB J 2010;24:4639–47.Google Scholar
Filiano, AJ, Martens, LH, Young, AH, Warmus, BA, Zhou, P, Diaz-Ramirez, G, et al. Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice. J Neurosci 2013;33:5352–61.Google Scholar
Bhaskar, K, Konerth, M, Kokiko-Cochran, ON, Cardona, A, Ransohoff, RM, Lamb, BT. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 2010;68:1931.Google Scholar
Schneider, JA, Arvanitakis, Z, Bang, W, Bennett, DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 2007;69:2197–204.Google Scholar
Knopman, DS, Kramer, JH, Boeve, BF, Caselli, RJ, Graff-Radford, NR, Mendez, MF, et al. Development of methodology for conducting clinical trials in frontotemporal lobar degeneration. Brain 2008;131:2957–68.Google Scholar
Scherling, CS, Hall, T, Berisha, F, Klepac, K, Karydas, A, Coppola, G, et al. Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol 2014;75:116–26.Google Scholar
Landqvist Waldö, M, Frizell Santillo, A, Passant, U, Zetterberg, H, Rosengren, L, Nilsson, C, et al. Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia. BMC Neurol 2013;13:54.Google Scholar
Whitwell, JL, Weigand, SD, Gunter, JL, Boeve, BF, Rademakers, R, Baker, M, et al. Trajectories of brain and hippocampal atrophy in FTD with mutations in MAPT or GRN. Neurology 2011;77:393–8.Google Scholar
Bateman, RJ, Xiong, C, Benzinger, TL, Fagan, AM, Goate, A, Fox, NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 2012;367:795804.CrossRefGoogle ScholarPubMed

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