Makoto Ishii
University of Texas Southwestern Medical Center, TX·Neuroscience
Alzheimer's disease is known for memory loss, but many patients also lose weight without trying, often before thinking problems appear. Weight loss tracks with faster decline and higher mortality, while weight gain appears protective.
- Fields
Neuroscience
Medicine & Clinical Research
Physiology
- Topics
Alzheimer's disease
dementia
amyloid-beta
- Grants
- 1 known grant, through Dec 2026
What they work on
- Test whether amyloid-beta disrupts intracellular calcium balance in leptin-responsive NPY/AgRP neurons, hunger-promoting hypothalamic cells, as an early event in Alzheimer's disease, using genetic mouse models.
- Determine whether amyloid-beta disrupts hypothalamic networks that regulate systemic metabolism, using neurophysiological recordings, imaging and genomic profiling in mouse models.
- Test whether dysfunction of central leptin signaling, the brain's response to the fat-derived hormone that reports energy stores, is an early manifestation in human subjects with Alzheimer's disease.
More about the research
That pattern suggests the hypothalamus, the brain region controlling appetite, body weight and whole-body metabolism, may be damaged very early, during presymptomatic stages. The cellular and molecular reasons remain largely unexplored.
Why it matters
Unexplained weight loss often precedes memory decline in Alzheimer's disease and predicts faster progression. Clarifying how amyloid-beta disrupts the brain circuits that control body weight and metabolism could yield early indicators of disease and suggest new therapeutic directions for a condition with no effective disease-modifying treatment.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xiaoyong Yang
Yale University, CT·Physiology
Determine whether O-GlcNAc signaling in ventromedial hypothalamus neurons sets the body weight setpoint, using mice with increased or deleted O-GlcNAc transferase (OGT) and comprehensive physiological measurements of weight and glucose.
Jeffrey Nicholas Savas
Northwestern University, IL·Neuroscience
Build a dynamic map of how amyloid beta (Aβ) plaques form and change in the brains of aging Alzheimer's model mice, tracking distinct plaque classes and Aβ forms such as Aβ42 and Aβ38.
Han Tan
University of California-Irvine, CA·Neuroscience·Early-career
Test whether BNC2 neurons, leptin-sensing cells in the hypothalamic arcuate nucleus, control the function of glucose-regulating organs through direct nerve connections.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
Reach out
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