PreprintCommunicationVersion 1Preserved in Portico This version is not peer-reviewed
The MAPT Isoform 0N3R Is Essential for Human Brain Development and Intolerant to Haploinsufficiency – Loss of Function as Disease Mechanism for TAU Associated Disease
Version 1
: Received: 5 December 2023 / Approved: 6 December 2023 / Online: 7 December 2023 (14:56:39 CET)
How to cite:
Zempel, H. The MAPT Isoform 0N3R Is Essential for Human Brain Development and Intolerant to Haploinsufficiency – Loss of Function as Disease Mechanism for TAU Associated Disease. Preprints2023, 2023120513. https://doi.org/10.20944/preprints202312.0513.v1
Zempel, H. The MAPT Isoform 0N3R Is Essential for Human Brain Development and Intolerant to Haploinsufficiency – Loss of Function as Disease Mechanism for TAU Associated Disease. Preprints 2023, 2023120513. https://doi.org/10.20944/preprints202312.0513.v1
Zempel, H. The MAPT Isoform 0N3R Is Essential for Human Brain Development and Intolerant to Haploinsufficiency – Loss of Function as Disease Mechanism for TAU Associated Disease. Preprints2023, 2023120513. https://doi.org/10.20944/preprints202312.0513.v1
APA Style
Zempel, H. (2023). The MAPT Isoform 0N3R Is Essential for Human Brain Development and Intolerant to Haploinsufficiency – Loss of Function as Disease Mechanism for TAU Associated Disease. Preprints. https://doi.org/10.20944/preprints202312.0513.v1
Chicago/Turabian Style
Zempel, H. 2023 "The MAPT Isoform 0N3R Is Essential for Human Brain Development and Intolerant to Haploinsufficiency – Loss of Function as Disease Mechanism for TAU Associated Disease" Preprints. https://doi.org/10.20944/preprints202312.0513.v1
Abstract
TAU is the main disease driver in Alzheimer’s and many other sporadic and genetic tauopathies. TAU is differently spliced, the role of individual splice-isoforms unclear. Murine Mapt-KO mice are healthy, and protected from Alzheimer’s, but no such case has been reported in humans. Using gnomad database, we here demonstrate that the only isoform expressed during fetal human brain development is intolerant to mutation, while other brain and peripheral nervous system TAU isoforms are dispensable. With TAU targeted therapies for Alzheimer’s and other tauopathies on the rise, we caution that TAU is essential human brain development.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
