Dataset Information

Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations.

ABSTRACT:

Objective

To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene.

Methods

We identified all subjects from Mayo Clinic, Rochester, Minnesota, that screened positive for mutations in MAPT and had a head MRI (n = 22). Voxel-based morphometry was used to assess patterns of gray matter atrophy in groups of subjects with the IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M mutations compared with age- and sex-matched controls.

Results

All MAPT groups showed gray matter loss in the anterior temporal lobes, with varying degrees of involvement of the frontal and parietal lobes. Within the temporal lobe, the subjects with IVS10+16, IVS10+3, N279K, and S305N mutations (mutations that influence the alternative splicing of tau pre-messenger RNA) all showed gray matter loss focused on the medial temporal lobes. In contrast to these groups, the subjects with P301L or V337M mutations (mutations that affect the structure of the tau protein) both showed gray matter loss focused on the lateral temporal lobes, with a relative sparing of the medial temporal lobe.

Conclusion

There seem to be differences in patterns of temporal lobe atrophy across the MAPT mutations, which may aid in the differentiation of the different mutation carriers. Furthermore, there seems to be a possible association between mutation function and pattern of temporal lobe atrophy.

SUBMITTER: Whitwell JL

PROVIDER: S-EPMC2754325 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations.

Whitwell J L JL Jack C R CR Boeve B F BF Senjem M L ML Baker M M Ivnik R J RJ Knopman D S DS Wszolek Z K ZK Petersen R C RC Rademakers R R Josephs K A KA

Neurology 20090901 13

<h4>Objective</h4>To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene.<h4>Methods</h4>We identified all subjects from Mayo Clinic, Rochester, Minnesota, that screened positive for mutations in MAPT and had a head MRI (n = 22). Voxel-based morphometry was used to assess patterns of gray matter atrophy in groups of subjects with the IVS10+16, IVS10+3, N279K, S305N, P3 ...[more]

PMID: 19786698

Similar Datasets

Project description:Background and objectiveMutations in the MAPT gene cause frontotemporal dementia (FTD). Most previous studies investigating the neuroanatomical signature of MAPT mutations have grouped all different mutations together and shown an association with focal atrophy of the temporal lobe. The variability in atrophy patterns between each particular MAPT mutation is less well-characterized. We aimed to investigate whether there were distinct groups of MAPT mutation carriers based on their neuroanatomical signature.MethodsWe applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning technique that identifies groups of individuals with distinct progression patterns, to characterize patterns of regional atrophy in MAPT-associated FTD within the Genetic FTD Initiative (GENFI) cohort study.ResultsEighty-two MAPT mutation carriers were analyzed, the majority of whom had P301L, IVS10+16, or R406W mutations, along with 48 healthy noncarriers. SuStaIn identified 2 groups of MAPT mutation carriers with distinct atrophy patterns: a temporal subtype, in which atrophy was most prominent in the hippocampus, amygdala, temporal cortex, and insula; and a frontotemporal subtype, in which atrophy was more localized to the lateral temporal lobe and anterior insula, as well as the orbitofrontal and ventromedial prefrontal cortex and anterior cingulate. There was one-to-one mapping between IVS10+16 and R406W mutations and the temporal subtype and near one-to-one mapping between P301L mutations and the frontotemporal subtype. There were differences in clinical symptoms and neuropsychological test scores between subtypes: the temporal subtype was associated with amnestic symptoms, whereas the frontotemporal subtype was associated with executive dysfunction.ConclusionOur results demonstrate that different MAPT mutations give rise to distinct atrophy patterns and clinical phenotype, providing insights into the underlying disease biology and potential utility for patient stratification in therapeutic trials.

Dataset Information

Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations.

Objective

Methods

Results

Conclusion

Publications

Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations.

Similar Datasets

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