Peter Nelson
University of Kentucky, KY·Neuroscience
About a quarter of people diagnosed with "Alzheimer's-type dementia" turn out at autopsy to have a different brain disease. It is called LATE (limbic-predominant age-related TDP-43 encephalopathy), and it is often accompanied by hippocampal sclerosis (HS), severe cell loss in a key memory region.
- Fields
Neuroscience
Medicine & Clinical Research
Pharmacology
- Topics
limbic-predominant age-related TDP-43 encephalopathy
hippocampal sclerosis
dementia
- Grants
- 1 known grant, through Jun 2027
What they work on
- Test whether the ABCC9 gene variant linked to LATE+HS risk lowers ABCC9 expression in human astrocytes, using RNA-Seq to map transcripts and splicing and immunohistochemistry on genotyped human brains.
- Test whether boosting the ABCC9/SUR2B channel protein only in astrocytes of TetR-TDP mice improves blood vessel function, measured by multiphoton imaging of neurovascular coupling and vessel leakiness and by MRI of cerebral blood flow.
- Measure how astrocyte-specific SUR2B upregulation changes brain metabolism in TetR-TDP mice, using astrocyte glutamate uptake, GCaMP calcium imaging and magnetic resonance spectroscopy of brain metabolites.
- Test whether nicorandil, an oral drug that opens KATP channels, improves memory in the radial arm water maze and Y-maze, astrocyte electrophysiology and neuropathology in TetR-TDP mice.
More about the research
A variant of the gene ABCC9 raises the risk of LATE+HS. ABCC9 makes a protein called SUR2, part of the KATP channel, an ion channel that acts as a metabolic sensor. It links low oxygen and stress in the brain to changes in cell calcium and blood flow. This project, part of a larger program project (P01), targets a mechanism in astrocytes, star-shaped support cells in the brain, with the goal of preventing this common form of dementia.
Why it matters
LATE with hippocampal sclerosis is present in about 25% of dementia cases diagnosed as Alzheimer's-type, and it has no targeted treatment. Nicorandil is already clinically safe and well tolerated. If it improves astrocyte and neuron function in mice, it could become a candidate for repurposing to prevent or slow this dementia in older adults, particularly those carrying the ABCC9 risk variant.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jingjing Liang
University of Arizona, AZ·Neuroscience
Test how Aggregatin, a protein encoded by the Alzheimer's-linked gene FAM222A, controls TDP-43 clumping and toxicity in neurons, using Aggregatin knockout models.
Todd A Fiacco
University of California-Riverside, CA·Neuroscience
Determine how much the volume-regulated anion channel in astrocytes contributes to brain tissue swelling and seizure generation in living mice, using astrocyte-specific conditional knockout animals.
Show-Ling Shyng
Oregon Health & Science University, OR·Biophysics
Solve cryo-EM structures of pancreatic, cardiac and vascular KATP channels in closed and open states, to build a complete set showing how the channels open in response to ATP and ADP.
The school
University of Kentucky: 34 labs on PI Pages, $528M a year on research, 319 research doctorates a year.
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