| Title |
The MAPT H1 haplotype is associated with tangle-predominant dementia
|
|---|---|
| Published in |
Acta Neuropathologica, July 2012
|
| DOI | 10.1007/s00401-012-1017-1 |
| Pubmed ID | |
| Authors |
Ismael Santa-Maria, Aya Haggiagi, Xinmin Liu, Jessica Wasserscheid, Peter T. Nelson, Ken Dewar, Lorraine N. Clark, John F. Crary |
| Abstract |
Tangle-predominant dementia (TPD) patients exhibit cognitive decline that is clinically similar to early to moderate-stage Alzheimer disease (AD), yet autopsy reveals neurofibrillary tangles in the medial temporal lobe composed of the microtubule-associated protein tau without significant amyloid-beta (Aβ)-positive plaques. We performed a series of neuropathological, biochemical and genetic studies using autopsy brain tissue drawn from a cohort of 34 TPD, 50 AD and 56 control subjects to identify molecular and genetic signatures of this entity. Biochemical analysis demonstrates a similar tau protein isoform composition in TPD and AD, which is compatible with previous histological and ultrastructural studies. Further, biochemical analysis fails to uncover elevation of soluble Aβ in TPD frontal cortex and hippocampus compared to control subjects, demonstrating that non-plaque-associated Aβ is not a contributing factor. Unexpectedly, we also observed high levels of secretory amyloid precursor protein α (sAPPα) in the frontal cortex of some TPD patients compared to AD and control subjects, suggesting differences in APP processing. Finally, we tested whether TPD is associated with changes in the tau gene (MAPT). Haplotype analysis demonstrates a strong association between TPD and the MAPT H1 haplotype, a genomic inversion associated with some tauopathies and Parkinson disease (PD), when compared to age-matched control subjects with mild degenerative changes, i.e., successful cerebral aging. Next-generation resequencing of MAPT followed by association analysis shows an association between TPD and two polymorphisms in the MAPT 3' untranslated region (UTR). These results support the hypothesis that haplotype-specific variation in the MAPT 3' UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD. |
Mendeley readers
The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 4% |
| Spain | 2 | 3% |
| Netherlands | 1 | 1% |
| Unknown | 64 | 91% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 20% |
| Researcher | 12 | 17% |
| Student > Master | 8 | 11% |
| Student > Doctoral Student | 5 | 7% |
| Student > Bachelor | 4 | 6% |
| Other | 13 | 19% |
| Unknown | 14 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 16 | 23% |
| Medicine and Dentistry | 11 | 16% |
| Neuroscience | 8 | 11% |
| Biochemistry, Genetics and Molecular Biology | 6 | 9% |
| Psychology | 4 | 6% |
| Other | 7 | 10% |
| Unknown | 18 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 July 2020.
All research outputs
#3,919,343
of 26,017,215 outputs
Outputs from Acta Neuropathologica
#999
of 2,635 outputs
Outputs of similar age
#24,085
of 167,369 outputs
Outputs of similar age from Acta Neuropathologica
#6
of 27 outputs
Altmetric has tracked 26,017,215 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,635 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.2. This one has gotten more attention than average, scoring higher than 59% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 167,369 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.