In vivo and Postmortem Clinicoanatomical Correlations in Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17
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Background: Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is associated with mutations in the Microtubule-Associated Protein Tau(MAPT) gene or the Progranulin(PGRN) gene. MAPT mutations lead to widespread deposition of hyperphosphorylated tau protein (FTDP-17T). PGRN mutations are associated with ubiquitin- and TDP-43-positive inclusions in the frontotemporal cortex, striatum and hippocampus (FTDP-17U). Despite the differences, FTDP-17T and FTDP-17U share a largely overlapping clinical phenotype. Objective: To determine whether neuroimaging studies may allow an in vivo early differentiation between FTDP-17T and FTDP-17U. Methods: We studied 25 individuals affected with FTDP-17T associated with either the exon 10+3 (24 subjects) or the G335S (1 subject) MAPT mutation, as well as 3 FTDP-17U individuals, who were carriers of the A9D, IVS6-2A>G or R493X PGRN mutation. Neuroimaging studies, obtained along the course of the disease, were compared to the neuropathologic findings. Results: FTDP-17T cases were associated with symmetric frontotemporal atrophy. Behavioral changes constituted the predominant clinical presentation. Conversely, an asymmetric degenerative process was seen in all 3 PGRN cases, who presented with either corticobasal syndrome (A9D) or frontotemporal dementia and language deterioration (IVS6-2A>G and R493X). Conclusion: Neuroimaging data, in the early disease stage of FTDP-17, may offer the possibility of an early differentiation of FTDP-17T and FTDP-17U phenotypes, independent of the genetic analysis.
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Structural MRI studies have shown that NFT deposition is associated with grey matter atrophy resulting from neurodegeneration, and that different tauopathies display distinctive regional patterns of grey matter atrophy.
“Structural MRI studies have shown that NFT deposition is associated with grey matter atrophy that results from neurodegeneration and that different tauopathies display distinctive regional patterns of grey matter atrophy [5][6][7][8].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [6]
The Results and Discussion (page numbers unavailable) report MRI atrophy patterns alongside neuropathology: MAPT-associated tau disease showed largely symmetric frontotemporal atrophy, whereas PGRN-associated, tau-negative disease showed asymmetric degeneration. The paper does not establish an association specifically between NFT deposition and grey-matter atrophy, or compare distinctive atrophy patterns across different tauopathies. (LLM, conf=0.85)
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References 15 · Cited by 28
Research works printed but not linked: 13
- Cruts M, Gijselinck I, van der Zee J, Engel- borghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Ku- mar-Singh S, Van Broeckhoven C: Null mu- tations in progranulin cause ubiquitin-posi- tive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442: 920- 924.
- Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P: Association of missense and 5 -splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998; 393: 702-705.
- Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D'Amato CJ, Gilman S: Frontotemporal dementia and parkinsonism linked to chro- mosome 17: a consensus conference. Ann Neurol 1997; 41: 706-715.
- van Swieten J, Spillantini MG: Hereditary frontotemporal dementia caused by Tau gene mutations. Brain Pathol 2007; 17: 63-73.
- Cairns NJ, Bigio EH, Mackenzie IR, Neu- mann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Tro- janowski JQ, Mann DM: Neuropathologic diagnostic and nosologic criteria for fronto- temporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol (Berl) 2007; 114: 5-22.
- Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MR, Ghetti B: Familial multiple system tauopathy with presenile de- mentia: a disease with abundant neuronal and glial tau filaments. Proc Natl Acad Sci USA 1997; 94: 4113-4118.
- Spina S, Murrell JR, Huey ED, Wassermann EM, Pietrini P, Baraibar MA, Barbeito AG, Troncoso JC, Vidal R, Ghetti B, Grafman J: Clinicopathologic features of frontotempo- ral dementia with progranulin sequence variation. Neurology 2007; 68: 820-827.
- Spina S, Murrell JR, Yoshida H, Ghetti B, Bermingham N, Sweeney B, Dlouhy SR, Crowther RA, Goedert M, Keohane C: The novel Tau mutation G335S: clinical, neuro- pathological and molecular characteriza- tion. Acta Neuropathol (Berl) 2007; 113: 461- 470.
- Spina S, Murrell JR, Huey ED, Wassermann EM, Pietrini P, Grafman J, Ghetti B: Cortico- basal syndrome associated with the A9D Progranulin mutation. J Neuropathol Exp Neurol 2007; 66: 892-900.
- Spina S, Farlow MR, Unverzagt FW, Kareken DA, Murrell JR, Fraser G, Epperson F, Crowther RA, Spillantini MG, Goedert M, Ghetti B: The tauopathy associated with mu- tation +3 in intron 10 of Tau: characteri- zation of the MSTD family. Brain 2008;131: 72-89.
- Snowden JS, Pickering-Brown SM, Macken- zie IM, Richardson AMT, Varma A, Neary D, Mann DMA: Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia. Brain 2006; 129: 3091-3102.
- Masellis M, Momeni P, Meschino W, Heff- ner R, Elder J, Sato C, Liang Y, St George- Hyslop P, Hardy J, Bilbao J, Black S, Rogaeva E: Novel splicing mutation in the progranu- lin gene causing familial corticobasal syn- drome. Brain 2006; 129: 3115-3123.
- Mesulam M, Johnson N, Krefft TA, Gass JM, Cannon AD, Adamson JL, Bigio EH, Wein- traub S, Dickson DW, Hutton ML, Graff- Radford NR: Progranulin mutations in pri- mary progressive aphasia: the PPA1 and PPA3 families. Arch Neurol 2007; 64: 43-47.
- Authors
- Ghetti, B., Spina, S., Murrell, J. R., Huey, E. D., Pietrini, P., Sweeney, B., Wassermann, E. M., Keohane, C., Farlow, M. R., & Grafman, J.
- Affiliations
- Indiana University School of Medicine (US)
- University of Siena (IT)
- National Institutes of Health (US)
- University of Pisa (IT)
- University College Cork (IE)
- ORCID
- Venue
- Neurodegenerative Diseases
- Publisher
- S. Karger AG
- Published
- 2008
- Volume
- 5
- Issue
- 3-4
- Pages
- 215-217
- ISSN
- 1660-2854 (ISSN-L)
- 1660-2862
- PMC
- PMC2826454
- OpenAlex
- W1993538200
- Cited by
- 28
- References
- 15
- Citations by year
- 2025: 1 · 2022: 1 · 2020: 1 · 2019: 3 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurodegenerative Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- Università degli Studi di Siena
- National Institutes of Health
- National Institute on Aging (AG 10133, P30AG010133)
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- MAPT mutations, progranulin mutations, hyperphosphorylated tau, TDP-43 inclusions, neuroimaging, neuropathology, frontotemporal atrophy, corticobasal syndrome, behavioral variant frontotemporal dementia, genotype-phenotype correlation
- MeSH terms
- Autopsy, Chromosomes, Human, Pair 17, Dementia, Humans, Language, Genetic Linkage, Mutation, Phenotype, Retrospective Studies, Syndrome, Parkinsonian Disorders
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