Top

Published in:

Open Access 01-11-2017 | Correspondence

Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia

Authors: Nicholas T. Olney, Carolina Alquezar, Eliana Marisa Ramos, Alissa L. Nana, Jamie C. Fong, Anna M. Karydas, Joanne B. Taylor, Melanie L. Stephens, Andrea R. Argouarch, Victoria A. Van Berlo, Deepika R. Dokuru, Elliott H. Sherr, Gregory A. Jicha, William P. Dillon, Rahul S. Desikan, Mary De May, William W. Seeley, Giovanni Coppola, Bruce L. Miller, Aimee W. Kao

Published in: Acta Neuropathologica | Issue 5/2017

Excerpt

A 52-year-old right-handed man presented for the evaluation of progressive emotional flattening, social withdrawal, and loss of empathy. Prior to symptom onset, his wife of 21 years described him as “easy going, loving, kind, and generous.” As symptoms progressed, the subject began to alienate coworkers with unwelcome and persistent practical jokes. These disinhibited behaviors were accompanied by new, compulsive Internet usage. No language, visuospatial, memory, or motor symptoms were reported. …

Available only for authorised users

Caccamo A, Magri A, Medina DX, Wisely EV, Lopez-Aranda MF, Silva AJ, Oddo S (2013) mTOR regulates tau phosphorylation and degradation: implications for Alzheimer’s disease and other tauopathies. Aging Cell 12:370–380. doi:10.1111/acel.12057 CrossRefPubMedPubMedCentral

Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol (Berl) 114:5–22CrossRef

Crino PB (2016) The mTOR signalling cascade: paving new roads to cure neurological disease. Nat Rev Neurol 12:379–392. doi:10.1038/nrneurol.2016.81 CrossRefPubMed

Curatolo P, Moavero R, de Vries PJ (2015) Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol 14:733–745. doi:10.1016/S1474-4422(15)00069-1 CrossRefPubMed

de Vries PJ, Whittemore VH, Leclezio L, Byars AW, Dunn D, Ess KC, Hook D, King BH, Sahin M, Jansen A (2015) Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist. Pediatr Neurol 52:25–35. doi:10.1016/j.pediatrneurol.2014.10.004 CrossRefPubMed

Doudna JA, Charpentier E (2014) Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096. doi:10.1126/science.1258096 CrossRefPubMed

Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Cena V, Gallego C, Comella JX (2000) Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 75:991–1003CrossRefPubMed

Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149:274–293. doi:10.1016/j.cell.2012.03.017 CrossRefPubMedPubMedCentral

Lipton JO, Sahin M (2014) The neurology of mTOR. Neuron 84:275–291. doi:10.1016/j.neuron.2014.09.034 CrossRefPubMedPubMedCentral

10.

Nixon RA (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983–997. doi:10.1038/nm.3232 CrossRefPubMed

11.

Qin W, Chan JA, Vinters HV, Mathern GW, Franz DN, Taillon BE, Bouffard P, Kwiatkowski DJ (2010) Analysis of TSC cortical tubers by deep sequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events. Brain Pathol 20:1096–1105. doi:10.1111/j.1750-3639.2010.00416.x CrossRefPubMedPubMedCentral

12.

Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477. doi:10.1093/brain/awr179 CrossRefPubMedPubMedCentral

13.

Sarnat HB, Flores-Sarnat L (2015) Infantile tauopathies: hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma. Brain Dev 37:553–562. doi:10.1016/j.braindev.2014.08.010 CrossRefPubMed

14.

Siman R, Cocca R, Dong Y (2015) The mTOR inhibitor rapamycin mitigates perforant pathway neurodegeneration and synapse loss in a mouse model of early-stage alzheimer-type tauopathy. PLoS ONE 10:e0142340. doi:10.1371/journal.pone.0142340 CrossRefPubMedPubMedCentral

15.

Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, Rossi G, Pareyson D, Mole SE, Staropoli JF et al (2012) Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet 90:1102–1107. doi:10.1016/j.ajhg.2012.04.021 CrossRefPubMedPubMedCentral

16.

Tang Z, Ioja E, Bereczki E, Hultenby K, Li C, Guan Z, Winblad B, Pei JJ (2015) mTor mediates tau localization and secretion: implication for Alzheimer’s disease. Biochim Biophys Acta 1853:1646–1657. doi:10.1016/j.bbamcr.2015.03.003 CrossRefPubMed

Title: Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia
Authors: Nicholas T. Olney
Carolina Alquezar
Eliana Marisa Ramos
Alissa L. Nana
Jamie C. Fong
Anna M. Karydas
Joanne B. Taylor
Melanie L. Stephens
Andrea R. Argouarch
Victoria A. Van Berlo
Deepika R. Dokuru
Elliott H. Sherr
Gregory A. Jicha
William P. Dillon
Rahul S. Desikan
Mary De May
William W. Seeley
Giovanni Coppola
Bruce L. Miller
Aimee W. Kao
Publication date: 01-11-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 5/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1764-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia

Excerpt

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Excerpt

Please log in to get access to this content

Other articles of this Issue 5/2017

α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading

Remodeling of heterochromatin structure slows neuropathological progression and prolongs survival in an animal model of Huntington’s disease

Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing

Medulloblastoma: experimental models and reality

Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology

Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome