The tauopathy associated with mutation +3 in intron 10 of Tau

Characterization of the MSTD family

Salvatore Spina, Martin Farlow, Frederick Unverzagt, David Kareken, Jill R. Murrell, Graham Fraser, Francine Epperson, R. Anthony Crowther, Maria G. Spillantini, Michel Goedert, Bernardino Ghetti

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Multiple system tauopathy with presenile dementia (MSTD) is an inherited disease caused by a (g) to (a) transition at position +3 in intron 10 of Tau. It belongs to the spectrum of frontotemporal dementia and parkinsonism linked to chromosome 17 with mutations in Tau (FTDP-17T). Here we present the longitudinal clinical, neuropsychological, neuroimaging, neuropathological, biochemical and genetic characterization of the MSTD family. Presenting signs were consistent with the behavioural variant of frontotemporal dementia in 17 of 21 patients. Two individuals presented with an atypical form of progressive supranuclear palsy and two others with either severe postural imbalance or an isolated short-term memory deficit. Memory impairment was present at the onset in 15 patients, with word finding difficulties and stereotyped speech also being common. Parkinsonism was first noted 3 years after the onset of symptoms. Neuroimaging showed the most extensive grey matter loss in the hippocampus, parahippocampal gyrus and frontal operculum/insular cortex of the right hemisphere and, to a lesser extent, in the anterior cingulate gyrus, head of the caudate nucleus and the posterolateral orbitofrontal cortex and insular cortex bilaterally. Neuropathologically, progressive nerve cell loss, gliosis and coexistent neuronal and/or glial deposits consisting mostly of 4-repeat tau were present in frontal, cingulate, temporal and insular cortices, white matter, hippocampus, parahippocampus, basal ganglia, selected brainstem nuclei and spinal cord. Tau haplotyping indicated that specific haplotypes of the wild-type allele may act as modifiers of disease presentation. Quantitative neuroimaging has been used to analyse the progression of atrophy in affected individuals and for predicting disease onset in an asymptomatic mutation carrier. This multidisciplinary study provides a comprehensive description of the natural history of disease in one of the largest known families with FTDP-17T.

Original languageEnglish
Pages (from-to)72-89
Number of pages18
JournalBrain
Volume131
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Tauopathies
Frontotemporal Dementia
Introns
Neuroimaging
Cerebral Cortex
Mutation
Gyrus Cinguli
Parkinsonian Disorders
Hippocampus
Parahippocampal Gyrus
Chromosomes, Human, Pair 17
Gliosis
Caudate Nucleus
Memory Disorders
Frontal Lobe
Temporal Lobe
Basal Ganglia
Prefrontal Cortex
Short-Term Memory
Neuroglia

Keywords

  • Frontotemporal dementia
  • Hippocampus
  • Progressive supranuclear palsy
  • Tau haplotype
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The tauopathy associated with mutation +3 in intron 10 of Tau : Characterization of the MSTD family. / Spina, Salvatore; Farlow, Martin; Unverzagt, Frederick; Kareken, David; Murrell, Jill R.; Fraser, Graham; Epperson, Francine; Crowther, R. Anthony; Spillantini, Maria G.; Goedert, Michel; Ghetti, Bernardino.

In: Brain, Vol. 131, No. 1, 01.2008, p. 72-89.

Research output: Contribution to journalArticle

Spina, S, Farlow, M, Unverzagt, F, Kareken, D, Murrell, JR, Fraser, G, Epperson, F, Crowther, RA, Spillantini, MG, Goedert, M & Ghetti, B 2008, 'The tauopathy associated with mutation +3 in intron 10 of Tau: Characterization of the MSTD family', Brain, vol. 131, no. 1, pp. 72-89. https://doi.org/10.1093/brain/awm280
Spina, Salvatore ; Farlow, Martin ; Unverzagt, Frederick ; Kareken, David ; Murrell, Jill R. ; Fraser, Graham ; Epperson, Francine ; Crowther, R. Anthony ; Spillantini, Maria G. ; Goedert, Michel ; Ghetti, Bernardino. / The tauopathy associated with mutation +3 in intron 10 of Tau : Characterization of the MSTD family. In: Brain. 2008 ; Vol. 131, No. 1. pp. 72-89.
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