Related Experiment Video
Updated: Aug 19, 2025
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
18.5K
Tuberous sclerosis complex is associated with a novel human tauopathy
Ji-Hye L Hwang1, Olga S Perloff1, Stephanie E Gaus1
1Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Acta Neuropathologica
|December 5, 2022
Summary
Tuberous sclerosis complex (TSC) patients may develop a unique tauopathy, characterized by neurofibrillary tangles, in mid-life. This TSC tauopathy shows distinct molecular features and occurs independently of other common protein pathologies.
Area of Science:
- Neuropathology
- Neurogenetics
- Molecular Biology
Background:
- Tuberous sclerosis complex (TSC) is a neurogenetic disorder caused by mutations in TSC1 or TSC2 genes, leading to varied neurological issues.
- While epilepsy is common in TSC, the neuropathological changes, especially dementia-related, in adults remain underexplored.
Purpose of the Study:
- To systematically examine neuropathological findings in adults with TSC.
- To investigate the presence and characteristics of tauopathy in TSC and compare it with non-TSC epilepsy and control groups.
Main Methods:
- Neuropathological examination of brain tissue from 11 adults with TSC (aged 30-58), 9 with non-TSC epilepsy, and 10 controls.
- Immunohistochemistry was used to detect neurofibrillary tangles, amyloid beta, TDP-43, alpha-synuclein, and specific tau post-translational modifications.
Main Results:
- A unique neurofibrillary tangle-predominant tauopathy, termed "TSC tauopathy," was identified in 3 of 11 TSC subjects.
- This TSC tauopathy occurred without pathological amyloid beta, TDP-43, or alpha-synuclein.
- Distinct patterns of tau acetylation and phosphorylation were observed, differing between TSC1 and TSC2 mutation carriers, with a 3-repeat tau isoform predominance.
Conclusions:
- Adults with TSC are at risk for developing a distinct mid-life tauopathy.
- The pathogenesis of TSC tauopathy appears linked to TSC1, TSC2, and associated molecular pathways.
- This tauopathy presents unique biochemical and molecular characteristics compared to other neurodegenerative tauopathies.
