Roberta Eileen Brinton
University of Arizona, AZ·Neuroscience
Women face about twice the lifetime risk of Alzheimer's disease (AD) as men, and the midlife transition into menopause may be part of the reason. As estrogen levels fall, the brain's ability to use glucose, its main fuel, can decline, and several early warning signs of Alzheimer's can appear.
- Fields
Neuroscience
Medicine & Clinical Research
Pharmacology
- Topics
Alzheimer's disease
menopause
women's health
- Grants
- 5 known grants, through Aug 2027
What they work on
- Test in a Phase 2 double-blind, placebo-controlled trial whether PhytoSERM, a plant-derived estrogen receptor beta (ERβ) modulator, preserves brain glucose metabolism in women with menopausal symptoms, measured by FDG-PET brain scans.
- Measure PhytoSERM's effects on cognition, hot flashes, sleep and mood, and on MRI outcomes such as gray matter volume, white matter integrity, brain connectivity and blood flow, along with blood biomarkers of Alzheimer's risk.
- Determine whether weekly intravenous allopregnanolone (Allo), a brain-made steroid that promotes new neurons, slows cognitive decline on the ADAS-cog14 test in APOE4 carriers with mild Alzheimer's, using a placebo-controlled, delayed-start Phase 2 trial.
- Develop MRI markers of hippocampal regeneration and connectivity, and a blood-based test that predicts Allo responders, using participant-derived iPSC neural stem cells, blood immune cells, CD34+ cells and mitochondrial respiration.
- Test whether estrogen's control of the brain's energy system requires coordinated gene expression from both the nuclear and mitochondrial genomes, plus rapid cytoplasmic signaling that provides real-time feedback on energy production.
- Test whether loss of estrogen in the aging female brain causes nuclear and mitochondrial gene control to come apart, followed by a decline in the mechanisms that sense the brain's energy demand and performance.
- Investigate how immune signaling in the brain and body drives Alzheimer's-related changes and peripheral autoimmunity during perimenopause, using mouse models carrying human versions of the APOE risk gene.
- Track how early-stage Alzheimer's develops in women moving from perimenopause to postmenopause, using multi-modal brain imaging and blood biomarkers to define neuro-immune markers of each stage of brain aging.
- Oversee regulatory compliance and data quality for human studies in the Precision Aging Network through standard operating procedures, audits, staff training and real-time monitoring of specimen and data collection.
More about the research
These grants follow that idea from basic biology to the clinic. They ask how estrogen keeps the female brain's energy system running and what happens when estrogen is lost. They ask how the perimenopausal transition interacts with genetic risk and the immune system. And they test whether two candidate therapies can protect or restore brain function in clinical trials.
Why it matters
In the US, aged women are expected to outnumber aged men two to one, and women carry about twice the risk of Alzheimer's. This work could give women going through menopause a safer hormone alternative, PhytoSERM, intended to ease symptoms and protect brain metabolism while avoiding estrogen-associated growth in breast tissue. It could also offer people with early Alzheimer's a regenerative treatment, allopregnanolone. Imaging and blood biomarkers could help identify women at risk earlier and guide precision prevention. Understanding estrogen's role in brain energy may also inform conditions more common after menopause, such as depression and multiple sclerosis.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Pauline Maki
Washington University in St Louis, MO·Neuroscience
Map longitudinal changes in brain structure, function, connectivity and memory across menopause stages in 220 women aged 40–59, staging menopause by bleeding criteria and anti-Müllerian hormone (AMH), and relating changes to estradiol.
Brandilyn Peters
Albert Einstein College of Medicine, NY·Public Health & Epidemiology
Determine how 12 weeks of transdermal estradiol, with or without progesterone, changes the gut microbiome of women with HIV in the randomized HoT trial, using shotgun metagenomic sequencing of stool samples.
Fei Yin
University of Arizona, AZ·Neuroscience
Determine how APOE variants, including APOE4, shift energy metabolism differently in neurons and astrocytes, using single-cell transcriptomics (gene-activity profiles of single cells) and functional tests in cultured cells.
The school
University of Arizona: 36 labs on PI Pages, $1.0B a year on research, 487 research doctorates a year.
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