Jonathan Kipnis
Washington University in St Louis, MO·Neuroscience
The brain is wrapped in thin protective layers called the meninges. These border tissues hold immune cells and lymphatic vessels, the drainage channels that carry cerebrospinal fluid (CSF), the clear fluid that bathes the brain, out toward the lymph nodes.
- Fields
Neuroscience
Microbiology & Immunology
Medicine & Clinical Research
- Topics
Alzheimer's disease
cerebral amyloid angiopathy
dementia
- Grants
- 5 known grants, through May 2030
What they work on
- Determine whether failing meningeal lymphatic vessels speed up the aging of nearby meningeal blood vessels, using imaging, surgical and drug-based methods in aged mice and AD mouse models.
- Define how immune cells in the meninges change when the meningeal blood vessels and lymphatic vessels fail, and check selected findings in human dura samples from fresh autopsies.
- Test several therapeutic approaches that boost healthy meningeal immunity, or target immune signaling molecules directly, to improve memory and cognition in aged mice and Alzheimer's disease models.
- Test whether IFNγ, an inflammatory signal made by aging CD4 and CD8 T cells in the meninges, acts directly on its receptors on lymphatic vessels to impair cerebrospinal fluid drainage in mice.
- Test whether antibodies that neutralize IFNγ and related cytokines can preserve meningeal lymphatic function in aged mice, reduce age-related brain dysfunction and strengthen existing AD immunotherapies.
- Test whether aging turns parenchymal border macrophages (scavenger cells lining brain vessels) inflammatory, causing extracellular matrix buildup that slows cerebrospinal fluid flow and traps amyloid beta in vessel walls.
- Test whether manipulating parenchymal border macrophages, for example with the growth signal M-CSF, restores cerebrospinal fluid flow and reduces Alzheimer's and cerebral amyloid angiopathy pathology in mice.
- Design CARdinal CAR T cells that home to amyloid beta plaques and other AD brain targets and then multiply and persist there through cytokine signaling, instead of killing their targets.
- Test whether CAR T cells that secrete IL-4 and/or BDNF, a growth factor that supports neurons, are safe and effective in vivo, and use single-cell multiomics to measure how they reprogram microglia and prevent cognitive decline.
More about the research
As we age, this drainage slows and the immune cells at the brain's borders change. Aging is also the biggest risk factor for Alzheimer's disease (AD), a dementia with no therapy that restores memory. The research asks how immune cells and drainage vessels at the brain's edges influence memory, waste clearance and Alzheimer's disease. It also asks whether these cells and vessels can be repaired or redirected as treatments. The projects range from how aging reshapes the meninges, to specific immune cells that slow fluid flow, to engineered immune cells built to deliver protective molecules into the brain.
Why it matters
Alzheimer's disease, cerebral amyloid angiopathy and other forms of age-related dementia have no treatments that reliably preserve memory. Current antibody drugs reduce amyloid plaques but have limited effects on cognition. This work could point to new treatment targets at the brain's borders, including meningeal lymphatic vessels, IFNγ released by aged T cells, and border macrophages that control fluid flow. It also proposes engineered T cells that could deliver neuron-protecting molecules directly to sites of disease in patients with Alzheimer's.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Amal Khalil Kaddoumi
Augusta University, GA·Pharmacology
Compare how well racemic etodolac and its R- and S-forms improve a cell-based blood-brain barrier model with amyloid-β pathology, measuring barrier permeability, Aβ clearance and RNA expression changes across doses.
Yunjie Tong
Purdue University, IN·Neuroscience
Measure how strongly changes in cerebral blood volume, the amount of blood in the brain, are coupled to cerebrospinal fluid (CSF) movement during both wake and sleep states.
Akihiko Urayama
University of Texas Health Science Center at Houston, TX·Neuroscience
Determine how chimeric versions of aducanumab and lecanemab are cleared from the brain in Alzheimer's model mice, and why clearance slows with age.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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