USC Scientists Target cPLA2 Enzyme to Halt Brain Inflammation in APOE4 Carriers, Backed by $3 Million Pattiz Foundation Gift
核心洞察
USC Center for Personalized Brain Health researchers have identified the enzyme cPLA2 (搜索) as a key driver of neuroinflammation in APOE4 (搜索) carriers who progress to Alzheimer's dementia.
The Norman and Mary Pattiz Foundation (搜索) has donated $3 million to the Keck School of Medicine of USC to accelerate drug discovery, AI-driven small molecule screening, and early detection efforts.
The funding establishes a high-risk registry combining APOE4 (搜索) genetic data with cardiovascular risk factors and supports neuropathologist Dr. Anne Hiniker in screening over 1,100 brain tissue samples for inflammatory markers.
An interdisciplinary team at the USC Center for Personalized Brain Health (CPBH) has identified a promising therapeutic pathway to prevent Alzheimer's disease (搜索) by targeting brain inflammation in individuals carrying the APOE4 (搜索) gene variant—the most significant genetic risk factor for late-onset Alzheimer's. The research, led by CPBH director Hussein Yassine, MD, now has a major new backer: the Norman and Mary Pattiz Foundation (搜索), which has committed $3 million to the Keck School of Medicine of USC to accelerate novel drug discovery and early detection initiatives.
The newly created Norman and Mary Pattiz Alzheimer's Research Fund will provide pilot funding and fast-track priority projects at the USC Alzheimer's Disease (搜索) Research Center (ADRC). The fund supports drug targeting efforts, imaging modality development, and the deployment of artificial intelligence to identify small molecules involved in brain inflammation. It will also modernize the center's brain pathology library and enable the examination of brain inflammation markers in Alzheimer's patients.
"We are extremely grateful to the Norman and Mary Pattiz Foundation (搜索) for having the foresight to support research that is breaking new ground," said Helena Chang Chui, MD, director of the ADRC and the Raymond and Betty McCarron Professor of Neurology. "That willingness to explore bold hypotheses is what has helped us to make headway in neurodegenerative diseases over the last several years."
The cPLA2 (搜索) Inflammatory Switch
The APOE4 (搜索) gene variant acts as a molecular tripwire rather than a guaranteed sentence for Alzheimer's. One of the primary mechanisms through which APOE4 damages cognitive tissue is by unleashing chronic, low-grade neuroinflammation years before structural memory loss appears. In a CPBH study examining differences among APOE4 carriers, Dr. Yassine's team discovered that individuals with elevated levels of the enzyme calcium-dependent phospholipase A2 (cPLA2 (搜索)) developed dementia.
With his collaborators, Dr. Yassine subsequently identified possible drug therapies capable of selectively targeting cPLA2 (搜索) while protecting normal cellular function from adverse effects. The team now aims to expand on this discovery to find additional targets that trigger neuroinflammation, with potential for developing new Alzheimer's drugs.
"Our goal is to determine whether these possible targets and treatment pathways are safe, feasible, and ultimately meaningful for human disease," said Dr. Yassine. "Thanks to the generosity of the Norman and Mary Pattiz Foundation (搜索), we have a better chance of pursuing these critical questions and finding the answers that can lead us forward."
AI-Powered Drug Discovery and Early Detection Registry
The Pattiz Fund will heavily support advanced artificial intelligence models designed to rapidly scan and screen thousands of small molecules, identifying compounds capable of crossing the blood-brain barrier and blocking inflammatory enzymes. Complementing this computational approach, USC will build a specialized early-detection registry mapping individuals at extreme risk for neuroinflammation. Candidates will be recruited by pairing APOE4 (搜索) genetic data with known cardiovascular risk factors through two established USC networks: GeneScreen, an Alzheimer's prevention registry focused on identifying genetic risk, and CPBH SPARK, a registry examining how lifestyle and health influences brain aging and Alzheimer's risk.
Neuropathology Core and Tissue Analysis
The Foundation's support also establishes the Norman and Mary Pattiz Foundation (搜索) Endowed Associate Professorship in Neuropathology, with Anne Hiniker, MD, PhD, director of the USC ADRC Neuropathology Core, named as the inaugural holder. The funding provides Dr. Hiniker with protected research time to accelerate the capture of inflammation markers across more than 1,100 brain tissue samples housed in the USC ADRC Neuropathology Core.
"I am honored to serve as the inaugural Pattiz Endowed Associate Professor," said Dr. Hiniker. "We hope to do justice to the legacy of Norman and Mary Pattiz with ambitious work designed to set the stage for new therapies for Alzheimer's disease (搜索)."
Honoring a Legacy of Innovation
Norman Pattiz, who founded Westwood One in 1976 and built it into the nation's largest radio network, and his wife Mary Turner Pattiz, a legendary Los Angeles rock DJ known as "The Burner" who later earned a PhD in clinical psychology and chaired the Hazelden Betty Ford Foundation, passed away in 2022 and 2023 respectively. The Board of Directors they entrusted to direct their philanthropic legacy previously funded an endowed chair in ovarian cancer research at the USC Norris Comprehensive Cancer Center.
"Norman and Mary Pattiz were trailblazers in their respective careers, and we hope to honor their legacy by carrying that same spirit of innovation and determination into the fight against Alzheimer's disease (搜索)," said Karen Kerrigan, Pattiz Foundation Board President.
Larry Freeman, a longtime USC supporter and Foundation Board member, added: "Each of our Board members has had personal experience with a loved one being impacted by Alzheimer's disease (搜索). We feel certain Norman and Mary would be excited about the potential impact this gift can have in the quest for solutions to this devastating disease."