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KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss.
- Source :
-
Journal of Clinical Investigation . 2/1/2024, Vol. 134 Issue 3, preceding p1-18. 19p. - Publication Year :
- 2024
-
Abstract
- Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase M? (PKM?) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NEUROPLASTICITY
*MEMORY loss
*ALZHEIMER'S disease
*TAUOPATHIES
*TAU proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 134
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 175324387
- Full Text :
- https://doi.org/10.1172/JCI169064