Faculty
John E. Donahue
, M.D.
Assistant Professor:
Pathology & Laboratory Medicine and Neurology
Phone: +1 401 444 5057
John_Donahue@Brown.EDU
Read John E. Donahue's full Faculty Research Profile.
Research Interests
While there is a growing body of evidence to indicate that the blood-brain barrier (BBB) is compromised in Alzheimer's disease (AD), there has been little data to support a link between known risk factors for AD and the BBB. My research will attempt to show that the product of the ε4 allele of the APOE gene, a known risk factor for developing AD, somehow fails to maintain the integrity of the BBB, compared to the ε3 allele, and that this BBB failure leads to the chain of events resulting in AD.
Biography
John E. Donahue received his M.D. from Tufts University in 1992. He trained in neurology at Tufts-New England Medical Center and in neuropathology at Rhode Island Hospital. After spending four years at the New Jersey Neuroscience Institute as Director of Neuropathology, he returned to RIH/Brown Medical School in 2003 to practice clinical neuropathology and pursue academic research in neurodegenerative diseases (e.g. Alzheimer's disease) and the blood-brain barrier. Being both a neurologist and neuropathologist enables him to bring a clinical perspective to neuropathology material and an underlying pathologic understanding to clinical material. Translational research in neurodegenerative diseases is ideally-suited for a neurologist-neuropathologist like him. This is a very rare combination in the 21st century; most newly-trained neuropathologists are trained in general anatomic and surgical pathology, not neurology.
Interests
John E. Donahue, M.D. is a neurologist-neuropathologist who currently studies Alzheimer's disease (AD) and the blood-brain barrier (BBB). He has shown that the heparan sulfate proteoglycan agrin, an important component of the vascular basal lamina, is fragmented in AD brain capillaries. Furthermore, he has also demonstrated that there is an alteration of the distribution of BBB amyloid-beta transporters RAGE (receptor for advanced glycation endproducts) and LRP-1 (low-density lipoprotein receptor-related protein-1) in AD. RAGE, which transports amyloid into the brain, is upregulated in the microvasculature of AD brains, while LRP-1, which transports amyloid out of the brain, is downregulated, leading to a net influx of amyloid into AD brains, further worsening the disease. Given that apolipoprotein E (apoE) is essential for maintaining BBB integrity, and that the apoE4 allele is a known risk factor for AD, Dr. Donahue is currently hypothesizing that the apoE4 allele is not as effective at keeping the BBB sealed, compared with the more common apoE3 allele, thus leading to the chain of events resulting in AD.
Dr. Donahue aims to become an expert in the BBB, to understand that particular anatomic structure and how neurologic function occurs, or does not occur, because of it. The BBB is a very underdeveloped and underappreciated area of neuroscience; less than 5% of abstracts submitted to the Society for Neuroscience annual meeting involve BBB research, yet the BBB is critically important in that its function leads to function of the brain, and its dysfunction leads to dysfunction of the brain.