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NIHNATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKER01

The hsp90 Cochaperone FKBP51 Regulates tau Structure and Function

Active
Institution
University of South Florida, FL
Principal investigator
Laura J Blair
Funding
$14K
Duration
2011–2028
Open portfolio

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Abstract

Project Summary/Abstract Neuropsychiatric symptoms (NPS), like depression, are common early in Alzheimer’s disease (AD) and correlate with a faster decline in patients. NPS and cognitive deficits in AD have been linked with the accumulation of tau protein. Two independent studies associated an allelic variant in the 51kDa FK506-binding protein (FKBP51) with increased risk for depression in AD. FKBP51 also regulates tau accumulation and toxicity to nerve cells. We will use transgenic mouse models to determine if either removing or inhibiting FKBP51 in mice will be protective against tau accumulation. We will also study whether mice that have this risk variant in combination with tau accumulation are more vulnerable to NPS. The critical knowledge gained through this work will add to our understanding of the role of FKBP51 in regulating tau pathogenesis especially during disease progression. This work will have a positive impact in AD research as we will further validate FKBP51 as a target and characterize the molecular landscape associated with vulnerability to NPS in tauopathies.

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R01NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEaccumulationdepressiontauopathiestau proteintautau accumulationnpsvariant

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