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Faculty Research Labs

Wilcock Lab

Colorful scan showing VCIDThe laboratory of Donna Wilcock, PhD was established in 2011 with a focus on vascular contributions to cognitive impairment and dementia (VCID) and neuroinflammation in VCID and Alzheimer’s disease. We take a multi-faceted approach in the laboratory that ranges from primary cell cultures, multiple mouse models, all the way to human biospecimens including plasma, cerebrospinal fluid, and brain tissue. Through extensive collaborations within Stark Neurosciences Research Institute, Indiana University School of Medicine and around the world, we are advancing understanding of multi-etiology dementia that one day will contribute to a precision medicine approach to treat dementia. We have research projects studying both mechanism and treatment of VCID and Alzheimer's disease, and funded by National Institute of Neurological Disorders and Stroke and the National Institutes of Health.

Active Research

Although the approval of aducanamab and lecenemab, both anti-Aß immunotherapies, for the treatment of Alzheimer’s disease has provided great promise for the future of dementia treatment, there are still significant safety concerns regarding their use. Two decades ago, our group and others showed that anti-Aß immunotherapies resulted in microhemorrhages in transgenic mouse brains and since then, clinical trials have been plagued by vasogenic edema and microhemorrhages. Now termed amyloid related imaging abnormalities (ARIA), these events occur in a third of aducanamab trial participants and is a major concern regarding the continued use of anti-Aß immunotherapies. A part of the active research in the Wilcock laboratory leverages new mouse models of Alzheimer’s disease to evaluate cellular, molecular, and functional changes due to immunotherapies in order to determine the mechanisms behind ARIA.

A long-standing research focus of the Wilcock lab is the role of the neurovascular unit, specifically astrocyte end feet, and how their loss contributes to vascular contributions to cognitive impairment and dementia (VCID), one of the leading causes of dementia. Over the last ten years we have focused our studies on a mouse model of hyperhomocysteinemia (HHcy), generating a translationally relevant mouse model of VCID. Our time course studies revealed that neuroinflammation appeared early in HHcy induction, followed by MMP9 activation, astrocyte end foot loss and cognitive decline, then microhemorrhages, suggesting the loss of astrocyte end feet and neurovascular dysfunction are main contributors to cognitive decline. Based on this timeline of pathologies, we suspect that MMP9, a protease that targets both tight junctions in the cerebrovasculature and anchoring proteins at the astrocyte end feet, could be a key mediator of astrocyte end foot loss resulting in neurovascular impairment, ultimately culminating in cognitive impairment. Active research projects in the Wilcock lab are focused on testing this hypothesis using multiple mouse models and approaches.   

A common manifestation of small-vessel cerebrovascular pathology and a key subtype of vascular contributions to cognitive impairment and dementia (VCID) is diffuse white matter disease (DWD), yet the mechanism behind DWD remains unclear. Our group has recently identified placental growth factor (PlGF) as being strongly associated with diffuse white matter disease in humans as well as increased in blood brain barrier leakage in our mouse model of hyperhomocysteinemia (HHcy). Using both human VCID samples and our HHcy diet in a novel PlGF knock out mouse model, another ongoing project in the Wilcock lab is to determine the role of PlGF in diffuse white matter disease and VCID. 

Research Team

Principal Investigator
63805-Wilcock, Donna

Donna M. Wilcock, PhD

Barbara and Larry Sharpf Professor of Alzheimer's Disease Research

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64139-Weekman, Erica

Erica M. Weekman, PhD

Assistant Research Professor of Neurology

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64570-Foley, Kate

Kate E. Foley, PhD

Postdoctoral Fellow in Neurology

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Daniel Rivera, PhD

Postdoctoral Fellow in Neurology

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Katelynn E. Krick

Graduate Student

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Sherika N. Johnson

Laboratory Technician

Research Publications

Keep up with the most recent publications for the Wilcock lab.