Donna J. CrossDonna J. Cross, Ph.D.
Assistant Professor of Radiology, University of Washington, Seattle, recipient of a 2010 New Investigator Research Grant

The research of Dr. Donna J. Cross has been inspired by her own family's experience with dementia, as well as the support of
the Alzheimer's Association.

Research focus

Refinements in imaging technology are revolutionizing the study of Alzheimer's disease. Dr. Cross's team has been using such techniques to study brain abnormalities that may lead to dementia. These abnormalities damage brain cells in many ways – altering their structure and hindering their ability to communicate with one another. The researchers hope that by identifying compounds that may slow or stop brain cell damage, they can help prevent people at risk of Alzheimer's from developing the disease. In addition, Dr. Cross and colleagues have begun studying another factor that may promote dementia risk: mild traumatic brain injury (mTBI). Also known as a concussion, mTBI may include loss of consciousness for less than 30 minutes, and symptoms are usually temporary and clear up within hours, days or weeks. Multiple mild concussions may result in persistent symptoms that do not improve with time. The association between mTBI and increased risk for dementia is not clear. However, this question is a critical health care issue with tremendous socio-economic implications for the future.

Impact of Association funding
Dr. Cross is unequivocal when speaking of the impact that Alzheimer's Association funding has had on her work. "The Alzheimer's Association grant … has been the single most important factor in my ability to work independently in this field. It has allowed me to establish my lab and to initiate research that has led to three more NIH (National Institutes of Health) grant submissions and will result in several publications. Personally, it has probably made all the difference in my future success as an academic researcher."

Visualizing the Early Signs of Dementia

Dr. Cross received her Association grant for a study entitled "In Vivo Imaging of Axonal Transport Deficits in Alzheimer's Disease." Brain cells use long, arm-like appendages called axons to communicate with on another. This communication involves rapid electrical signals, which the axons both send and receive. But for axons to function properly, they must constantly get nutrients from other parts of the cell—a process known as axonal transport. Evidence shows that axonal transport becomes disrupted in the early stages of Alzheimer's disease, possibly because a protein called glycogen synthase kinase-3 (GSK-3) becomes abnormally active. GSK-3 is also linked to the production of an abnormal form of the protein tau in the brain. This abnormal form of tau impedes delivery of nutrients to axons and results in the development of tau tangles in the brain, another feature of early Alzheimer's.

Dr. Cross and colleagues are using magnetic resonance imaging (MRI) to determine how GSK-3 may hinder axonal transport in living mice. These mice are genetically engineered to express Alzheimer's-like pathologies. The team is taking advantage of a new, more powerful MRI scanner, which can visualize the process of axonal transport with unprecedented clarity and detail. The researchers are also testing whether lithium treatment may inhibit GSK-3 activity, maintain axonal function, and prevent or slow cognitive decline in the mice. Results of this work could help elucidate the role of GSK-3 in Alzheimer's disease, and they could identify lithium as an important drug therapy for preventing or slowing Alzheimer's-related cognitive loss.

Mild Traumatic Brain Injury and Cognitive Loss

The Alzheimer's Association has also helped Dr. Cross expand the focus of her research. Her team is now studying the effects of mTBI on cognitive loss and dementia. In May 2012, Dr. Cross was invited to attend a meeting entitled "Military Risk Factors for Alzheimer's Disease," which was co-organized by the Association and NCIRE - The Veteran's Health Research Institute. With many prominent scientists, military personnel and NIH administrators in attendance, this meeting focused on the neurological consequences of combat-related mTBI among veterans. Dr. Cross found the meeting "enormously helpful," and she has since acquired pilot funding to develop a novel treatment to "ameliorate the effects of brain injury." As she states, the "association between TBI and the increased risk for neurodegenerative disease is well established. There is a growing concern regarding the socio-economic impact of civilian and military mTBI in relation to the increased incidence of dementia in these populations."

Dr. Cross and colleagues have recently made considerable progress in this effort. They have devised a potential Alzheimer's therapy that targets the damage caused by mTBI, and they have applied for a provisional patent for this treatment.

A Motivated Researcher

Family history played a decisive role in Dr. Cross's choice of her research focus. During her early doctoral studies, both of her paternal grandparents were diagnosed with cognitive disorders—her grandmother with Alzheimer's and her grandfather with Parkinson's disease. She remembers her grandmother telling her "Hurry up and find a cure, Donna, I really need it!" Deeply motivated, Donna focused her studies on dementia research and became the first member of her family to earn a Ph.D. Even though her grandmother and grandfather died before she graduated, she notes that her "dissertation was dedicated to them as well as to my mentally healthy grandparents on my mother's side, who were still alive and so proud of me." Dr. Cross's family struggle with dementia is not unique. "Alzheimer's touches everyone at some level," she says, "and the loss of one's memories and one's self is the ultimate tragedy because that's what makes us human." Her mission to "hurry up and find a cure" may have been inspired by her grandparents' courage, but the growing impact of dementia on society at large continues to motivate her today.

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