Tim Huang awarded $4.3 million NIH grant to study the protective role of SORLA against Alzheimer’s disease and related tauopathies

Tim Huang, Ph.D. headshot

Research may further implicate SORLA as a novel therapeutic drug target for certain types of dementia.

Tim Huang has been awarded a new grant from the National Institutes of Health (NIH) to continue his work on understanding the protective role of SORLA—a genetic risk factor for Alzheimer’s Disease (AD). The five-year, $4.3 million project will further advance the study of SORLA as a potential therapeutic target for AD and related dementias.

“We’re helping to piece together how SORLA affects a protein called tau, which is found abundantly in the brain and nervous system,” says Huang, an assistant professor in the Degenerative Diseases Program at Sanford Burnham Prebys. “An abnormal buildup of tau likely contributes to neurodegeneration and cognitive decline in Alzheimer’s disease and other neurodegenerative conditions.”

Although the last decade established that SORLA plays a key role in reducing beta-amyloid—the main component of amyloid plaques found in the brains of people with AD—virtually nothing is currently known about whether SORLA can affect tau.

SORLA is an intracellular sorting receptor that directs cargo proteins, such as kinases, phosphatases and signaling receptors, to their correct location within the cell.

SORL1 (the gene encoding SORLA) is one of many recently described AD risk genes with variants associated with an increased risk of AD, which affects 5.5 million people in the U.S. The biggest risk factor is age—as the average life expectancy increases, the number of people with Alzheimer’s is expected to almost triple by 2050.

“This award is focused on determining whether and how SORLA can potentially enact a protective response to tau,” says Huang. “We will utilize a mouse model that expresses a mutant form of human tau to test whether modulation of SORLA levels can alter toxic effects related to tau.

“The work has the potential to help people affected by AD, as well as other tau-specific disorders (tauopathies) such as frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy.”

This research is in collaboration with Kevin Yip, Ph.D., a professor at Sanford Burnham Prebys.
 

The grant, awarded by the National Institute on Aging of the National Institutes of Health, is “Novel Neuroprotective Roles for the Alzheimer's Disease Risk Gene SORLA in Tau Pathology and Pathogenesis,” Award number: 1 R01 AG085498-01. 

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