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New Gladstone Institute Aims To Devise Therapies For Alzheimer's And Other Debilitating Brain Diseases

September 15, 1998
University Of California, San Francisco
A major new research venture that will focus solely on advancing scientific knowledge about brain diseases--such as Alzheimer's disease, HIV-associated dementia, and stroke--was inaugurated Sept. 11 in San Francisco.

A major new research venture that will focus solely on advancingscientific knowledge about brain diseases--such as Alzheimer's disease,HIV-associated dementia, and stroke--was inaugurated today (Sept. 11) in San Francisco.

The new center is the Gladstone Institute of Neurological Disease,operated by The J. David Gladstone Institutes in partnership with UC SanFrancisco.

Research will be directed at greater understanding of the biology ofneurological disease with the goal of speeding development of new treatment forsome of the most prevalent and incapacitating disorders.

Alzheimer's disease affects some four million Americans and is thefourth leading cause of death among adults in the United States. Dementia alsoafflicts a significant number of AIDS patients, and the National Institute onAging estimates that Americans suffer nearly 700,000 strokes each year.

The new venture brings together six principal investigators and thirteenadditional scientists from multiple disciplines who will pool their expertise. The new institute will be located at the UCSF-affiliated San Francisco GeneralHospital.

"We are in an excellent position to increase our understanding of theprocesses that result in neurological disease and to hasten the development oftherapies for these devastating conditions," said Lennart Mucke, MD, UCSFassociate professor of neurology and the institute's director. "I am veryexcited about the future."

The new institute will build on a 1992 discovery by Gladstoneresearchers that apolipoprotein E (apoE), a protein involved in cholesterolmetabolism, also has profound effects on the growth of nerve cells. Since then,other investigators have found that the inheritance of certain variations of theapoE gene is a significant risk factor for Alzheimer's disease.

"The establishment of this institute reflects the astonishing scientificmomentum that has already been achieved under Dr. Mahley's and Dr. Mucke'sleadership," said Haile T. Debas, MD, dean of the UCSF School of Medicine andvice chancellor for medical affairs. "UCSF is pleased to have this opportunityto expand an already fruitful collaboration with the Gladstone Institute."

The seed for the new institute was planted in 1996, when Mucke came toUCSF from the Scripps Research Institute in La Jolla, Calif., to direct thenewly created Gladstone Molecular Neurobiology Program.

The program, a collaborative effort with the UCSF Department ofNeurology, made such rapid progress in studies of Alzheimer's disease andHIV-associated dementia that the decision was made to significantly expand theeffort and create an entirely new enterprise, according to Robert W. Mahley, MD,PhD, UCSF professor of medicine and pathology and president of the GladstoneInstitutes.

Supported by a combination of outside resources and Gladstone funds, thenew institute will join the Gladstone Institute of Cardiovascular Disease andthe Gladstone Institute of Virology and Immunology, also located at SFGH. "Thismarks a significant step in the evolution of the Gladstone Institutes," saidMahley.

The Gladstone researchers have worked closely with their neurosciencecolleagues on the UCSF Parnassus campus and already have formed a Bay AreaAlzheimer's Disease Study Group that brings researchers from leading academicinstitutions to monthly meetings at UCSF and SFGH.

Under the University's current plans, the new institute will berelocated to UCSF's future Mission Bay campus. This move would allow closecollaborations between the Gladstone researchers and other neuroscientists atUCSF.

"Our program will contribute to the critical mass of scientists focusedon brain research and should form a vital link between basic and clinicalneuroscience on the new campus," Mahley said.

The investigators joining forces in the new institute have already madea number of important discoveries:

  • They have found, together with colleagues from other institutions,that so-called "amyloid proteins," which accumulate in brains of Alzheimer'spatients in the form of spider web-like deposits, can damage connections betweennerve cells that are important for normal brain function.
  • They have observed that molecules involved in brain inflammation afterstrokes and head injury can increase the accumulation of amyloid proteins in thebrain.
  • Most recently, a team of Gladstone neuroscientists have demonstratedthat apoE4, a protein that strongly increases the risk of developing Alzheimer'sdisease in humans, impairs memory and learning in mice. Study results werepublished September 1 in the Proceedings of the National Academy of Sciences. The animal models used in this research and others developed by Gladstoneinvestigators can be used to test the effectiveness and safety of new treatmentsbefore they are used in human patients.
  • In the AIDS field, Gladstone neuroscientists have shown that specificHIV proteins can disrupt the normal function of nerve cells and that, at leastin animal models, these effects can be blocked with medications that make nervecells less excitable.
  • The researchers showed that the human CD4 receptor, the entryway forHIV into immune cells, also may play a role in the degeneration of brain cellsin AIDS patients.

The new institute was inaugurated with a one-day scientific symposiumtoday (September 11) featuring distinguished neuroscientists from UCSF andaround the country. Among the speakers were Zach Hall, PhD, UCSF vicechancellor for research and former director of the National Institute ofNeurological Disorders and Stroke of the NIH, and Nobel Laureate StanleyPrusiner, MD, UCSF professor of neurology, who won the coveted prize in 1997 forhis work on prions, particles responsible for some forms of dementia.

"The diseases we study rob people of their memories and of the abilityto share thoughts with loved ones. These conditions are so frequent that, sooneror later, almost everybody is touched by one of them, either directly orindirectly through an afflicted relative or friend," Mucke said. "The newGladstone Institute of Neurological Disease will greatly strengthen UCSF's fightagainst these illnesses."

The J. David Gladstone Institutes are named for a prominent real estatedeveloper who died in 1971. His will created a testamentary trust that reflectshis long-standing personal interest in medical education.

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University Of California, San Francisco. "New Gladstone Institute Aims To Devise Therapies For Alzheimer's And Other Debilitating Brain Diseases." ScienceDaily. ScienceDaily, 15 September 1998. <>.
University Of California, San Francisco. (1998, September 15). New Gladstone Institute Aims To Devise Therapies For Alzheimer's And Other Debilitating Brain Diseases. ScienceDaily. Retrieved April 27, 2017 from
University Of California, San Francisco. "New Gladstone Institute Aims To Devise Therapies For Alzheimer's And Other Debilitating Brain Diseases." ScienceDaily. (accessed April 27, 2017).