Describing the diversity of MAPT transcripts in the parietal cortex of Pick’s disease patients

The tau protein-encoding gene, MAPT, undergoes complex alterative splicing that gives rise to several protein isoforms in the adult human brain. These differ in the inclusion or exclusion of exons 2, 3, and 10 located at the N- and C-terminals of the protein. Inclusion or exclusion of exon 10 produces 4-Repeat (4R) and 3-Repeat (3R) tau isoforms, respectively. While the altered protein ratios have been greatly described in the tauopathies, the evidence supporting the presence of changes at the transcript level has been inconsistent. We characterized MAPT alternative splicing patterns with long-read RNA sequencing (LR RNA-Seq) in a 3R tauopathy, Pick’s disease (PiD), which represents a rare sporadic primary tauopathy that affects younger individuals. Our data highlights the use of LR RNA-Seq to comprehensively characterize MAPT transcripts in the context of PiD, suggesting an intricate regulation of transcript expression that extends beyond the canonical transcripts.

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Publication Details

Journal
npj Dementia
Published
2025-09-04
DOI
https://doi.org/10.1038/s44400-025-00027-x
Primary Topic
RNA regulation and disease
Type
article
Field-Weighted Citation Impact
0.00

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article

Describing the diversity of MAPT transcripts in the parietal cortex of Pick’s disease patients

Nicole Tamvaka, Keith A. Josephs, Dennis W. Dickson, Michael G. Heckman et al.
npj Dementia
RNA regulation and disease
article

Describing the diversity of MAPT transcripts in the parietal cortex of Pick’s disease patients

Nicole Tamvaka, Keith A. Josephs, Dennis W. Dickson, Michael G. Heckman, Melissa E. Murray, Margaret L. Stuber, Marios Gavrielatos, Shanu F. Roemer, Bradley F. Boeve, Alexandra I. Soto‐Beasley, Owen A. Ross, Neill R. Graff‐Radford
article en

Abstract

The tau protein-encoding gene, MAPT, undergoes complex alterative splicing that gives rise to several protein isoforms in the adult human brain. These differ in the inclusion or exclusion of exons 2, 3, and 10 located at the N- and C-terminals of the protein. Inclusion or exclusion of exon 10 produces 4-Repeat (4R) and 3-Repeat (3R) tau isoforms, respectively. While the altered protein ratios have been greatly described in the tauopathies, the evidence supporting the presence of changes at the transcript level has been inconsistent. We characterized MAPT alternative splicing patterns with long-read RNA sequencing (LR RNA-Seq) in a 3R tauopathy, Pick’s disease (PiD), which represents a rare sporadic primary tauopathy that affects younger individuals. Our data highlights the use of LR RNA-Seq to comprehensively characterize MAPT transcripts in the context of PiD, suggesting an intricate regulation of transcript expression that extends beyond the canonical transcripts.

npj DementiaVol. 1(1)
Stimson Center (US), Jacksonville College (US), WinnMed (US), Paracelsus Medizinische Privatuniversität (DE), Mayo Clinic in Arizona (US), Mayo Clinic in Florida (US)
U.S. Department of Defense, Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Association, American Brain Foundation, CurePSP, Little Family Foundation, National Institutes of Health
Openalex Percentile: Top 79%
RNA regulation and disease
DOIOpen Access PDFOpenAlex
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