We are proud to support innovative, high-impact research into new ideas about the causes and treatment of dementias through our Pilot Project program. This program offers “kick-starter” research funding to junior investigators at the University of Michigan, Michigan State University, Wayne State University, and Veteran Affairs Ann Arbor Health System so that they can begin testing their ideas.
This year, we had a record number of applicants with more than 30 applications. We are very proud to award four of these seven awards from collaborations with statewide programs and institutions, including Michigan State University, Wayne State University, and the University of Michigan Claude Pepper Center.
Please join us in congratulating the 2019-2020 Pilot Project recipients:
Benjamin Singer, MD
University of Michigan
β-amyloid potentiates neuroinflammation and cognitive decline after sepsis survival
Project summary: Many families and doctors observe that patients with early symptoms of dementia, previously functioning well at home, lose their independence and have rapid progression of dementia after hospitalization for an infectious illness. This experience is borne out in epidemiologic studies, but the mechanism of the interaction is unknown. Dr. Singer’s laboratory uses animal models and human autopsy tissue to study mechanisms of brain injury and neuroinflammation that occur in survivors of acute medical illness, especially systemic infections and pneumonia. His laboratory will use this pilot award to test the hypothesis that early Alzheimer’s disease pathology and systemic infection interact synergistically to sustain a state of persistent, but potentially treatable, inflammation in the brain.
Patrick Pruitt, PhD
Wayne State University
Linking social isolation and cognition through functional brain network correlates in non-demented older adults
Project summary: Given the current lack of effective medicine for dementia, it is important to better understand behavioral factors that delay or prevent age-related cognitive decline. Interventions using social interactions are effective at enhancing cognitive performance in older adults; conversely, social isolation is a risk factor for dementia. Together, these observations suggest social engagement is an important aspect of healthy cognitive aging. But how is social engagement related to the function of major brain networks which support cognition? Answering this question will be critical as researchers and clinicians try to use social interactions to promote healthy cognition in older adults. Dr. Pruitt’s project will investigate the relationship between social isolation and disrupted connectivity within and between major brain networks. By identifying the disrupted connections associated with social isolation and poor cognitive performance, the team will shed light on brain mechanisms through which social isolation contributes to cognitive decline and establish these connections as critical targets for future interventions.
Benjamin Combs, PhD
Michigan State University
Amyloid potentiates neuroinflammation and cognitive decline after sepsis survival
Project summary: In Alzheimer’s disease, modified forms of tau protein can disrupt axonal transport, a critical process for maintaining the health and function of neurons. This project will examine functional interactions between tau and cytoplasmic dynein, the motor complex responsible for transport of material from the synapse to the cell body, to better understand the process by which modified tau disrupts axonal transport in disease. This study will further our understanding of toxic events in Alzheimer’s disease and may provide potential targets for the development of therapies to slow or stop disease progression.
Matthias Truttmann, PhD
University of Michigan
The impact of protein AMPylation on Alzheimer’s disease
Project summary: In Alzheimer’s disease, toxic protein aggregates (clumps) challenge and kill cells in our brains, triggering memory loss. Dr. Truttmann’s project aims to elucidate why these protein aggregates are toxic to cells. The team hypothesizes that protein aggregates found in Alzheimer’s disease challenge energy homeostasis in brain cells, which will eventually lead to their collapse. They will test this hypothesis using small nematode (worm) Alzheimer’s disease models that allow us to examine basic mechanisms of protein aggregation disorders. In these worms, they will examine 1) how the appearance of toxic protein aggregates affects cellular carbohydrate (sugar) and lipid (fat) consumption and 2) how protein aggregation-linked changes in cellular carbohydrate and lipid turn-over alters the performance, fitness and durability of neurons.
Scott Counts, PhD and Yu-Chung Norman Cheng
Michigan State University and Wayne State University, respectively
Magnetic properties of microvascular lesions as potential biomarkers for dementia
Project summary: Small bleeding or coagulated blood inside the brain appears in people with dementia. Those small bleeds also appear in people with stroke or traumatic brain injuries, of whom a certain fraction can become demented. As the number of small bleeds does not seem to be the deciding factor to diagnose dementia, this pilot project examines the magnetic properties and volumes of those small bleeds in brain samples from people with and without dementia. Drs. Counts and Cheng will measure magnetic properties and the volume of each small object from MRI images, and determine whether each object seen in MRI is a small bleed through histology examination. If a stronger magnetic property quantified from MRI reflects a higher concentration of blood in histology, especially from people with dementia, then the magnetic property of small bleeds may be a potential biomarker for some dementias.
Omar Ahmed, PhD
University of Michigan
Understanding retosplenial dysfunction in Alzheimer’s disease to identify novel therapeutic targets
Project summary: In the brain, the retrosplenial cortex is essential for the formation and recall of memories. It is also one of the first brain regions to show decreased activity in the earliest stages of Alzheimer’s disease. Despite its clear importance in memory formation, the retrosplenial cortex is understudied. We will combine multiple cutting-edge research technologies, including 3D holographic circuit mapping, to investigate the precise cells, circuits and brain rhythms that are specifically altered in Alzheimer’s disease. This work will help to identify novel molecular and cellular targets in the retrosplenial cortex for the treatment of Alzheimer’s disease.
University of Michigan
Towards a Culturally Responsive Intervention for Black Caregivers of Persons with Dementia
Project summary: Black family caregivers of persons with dementia have an increased risk for developing dementia themselves. A combination of stress and chronic diseases such as heart disease, diabetes, and high blood pressure contributes to both this risk, and to the risk of future disability. Evidence suggests that, in addition to regular cognitive testing, handgrip strength can tell us about cognitive decline. As work moves towards designing a highly effective intervention for Black caregivers, it is necessary to find the most efficient ways of gathering caregiver information and ensuring that the types of information we gather do not create too much of a burden on participating caregivers. In addition to gathering information about caregiver handgrip strength and cognition, this pilot study tests the ease of administering and completing an electronic survey about caregiver social support and personal health. Through this work, Dr. Robinson-Lane hopes to develop a culturally tailored program for dementia caregivers.
We look forward to seeing how this important research progresses in the coming year.