SAN DIEGO — Researchers are shedding light on neural mechanisms underlying the progression of Alzheimer's disease. These findings will be presented at Neuroscience 2025, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to symptoms including cognitive decline, memory loss, and the inability to perform daily functions. According to the Alzheimer's Association, it's estimated that 6.9 million Americans were living with AD in 2024; that number is expected to increase. Scientists are working to understand the signs of early disease in the brain before more severe pathologies, including amyloid plaques and neurofibrillary tangles, emerge.
Today’s new findings show that:
- Differences in neuronal excitation-inhibition (E-I) balance can differentiate human subjects with stable mild cognitive impairment (MCI) from those whose MCI progresses to AD, potentially enabling MCI-to-AD prediction. (Guoshi Li, University of North Carolina Chapel Hill)
- Gene expression and connections between brain cells were extensively rewired in the suprachiasmatic nucleus (SCN) — an area of the brain which controls sleep and biological rhythms — in a mouse model of AD. Disruptions in biological rhythms may appear early in AD. (Satchin Panda, Salk Institute)
- Mice with AD risk factors that slept less in midlife experienced memory decline as they aged, along with loss of a specific population of neurons involved in memory processing and sleep. (Frank Raven, University of Michigan)
- In an AD mouse model with humanized APP and APOE genes, a combination of FDA-approved therapies (atorvastatin, pioglitazone, tofacitinib) improved biomarkers of AD pathology, particularly in female mice. (Roberta Diaz Brinton, University of Arizona)
- RNA analysis showed that an AD mouse model with humanized APP and APOE genes exhibited changes in immune- and metabolic-related gene expression, particularly in female mice, suggesting an interplay between sex and APOE genotype. (Roberta Diaz Brinton, University of Arizona)
"As exciting as it is to see new disease-modifying treatments for Alzheimer’s becoming available, it’s equally important that we empower people with knowledge and tools to protect their own brain health. Evidence-based lifestyle choices can reduce the risk of Alzheimer’s and support long-term cognitive health,” said Sharyn Rossi, PhD, senior director of neuroscience programs at BrightFocus Foundation and moderator of the press conference. “Our role is not only to advance treatments, but also to ensure the public understands the steps they can take today to safeguard their brain health.”
For complete access to Neuroscience 2025 in-person and online, request media credentials. This research was supported by national funding agencies including the National Institutes of Health and private funding organizations.
Sunday, November 16, 2025
3–4 p.m. PST
San Diego Convention Center, Room 15A, and online for registered media
Alzheimer’s Disease Press Conference Summary
- These presentations examined the early stages of AD, from symptoms like mild cognitive impairment and problems with sleep and biological rhythms to sex-specific disease hallmarks and early combination therapies.
- Four out of the five studies used rodent models. One used a dataset collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database.
Prediction of mild cognitive impairment to Alzheimer's dementia using excitation-inhibition imbalance
Guoshi Li, guoshi_li@med.unc.edu, Abstract PSTR323.23
- Mild cognitive impairment (MCI), the decline of memory or cognitive abilities without change in daily functioning, can be an early warning sign of AD. But not all MCI progresses to AD.
- To identify the relationship between MCI and AD, scientists studied the contributions of excitatory and inhibitory synaptic inputs, or excitation-inhibition (E-I) balance. E-I balance is impaired in people with AD.
- Using a brain imaging dataset collected from the Alzheimer’s Disease Neuroimaging Initiative database, they applied a computational model to estimate E-I balance in stable MCI patients and MCI patients who developed AD. The program could distinguish between stable and progressive MCI individuals, suggesting E-I imbalance could be a biomarker for early diagnosis.
Impact of Alzheimer’s disease on suprachiasmatic nucleus connectivity, sleep regulation and circadian rhythm
Satchin Panda, panda@salk.edu, Abstract PSTR156.10
- Researchers studied an APP/PS1 mouse model containing genetic changes associated with AD. The animals showed symptoms of sleep and daily rhythm disruption, with less REM sleep and weaker cycles of metabolism and temperature.
- Scientists analyzed the brain region controlling these functions: the suprachiasmatic nucleus (SCN). While there was no loss of neurons, the cell connections and gene expression were altered compared to control animals. This suggests that sleep/rhythm problems may appear early in AD pathophysiology.
The night watch: how midlife sleep guards neural networks underlying memory in Alzheimer’s
Frank Raven, frankra@umich.edu, Abstract PSTR156.25
- Sleep problems in midlife are associated with increased risk of AD, but the biological relationship isn't clear.
- Using a genetically diverse set of mice that more effectively captures the variability of AD, researchers showed that mice that slept less in midlife had several distinct symptoms as they aged: more severe memory decline, more dramatic brain changes in areas involved in sleep and memory, and loss of somatostatin-positive (SST+) interneurons — cells needed for memory processing and sleep regulation.
- The results suggest that loss of this cell population could link poor sleep in midlife with later memory decline.
Impact of Combination Therapies on Alzheimer's Disease-Related Outcomes in a Humanized APP/APOE AD-Risk Model During Midlife
Roberta Diaz Brinton, rbrinton@arizona.edu, Abstract PSTR437.12
- While AD is a disorder of the brain, dysregulated glucose metabolism, lipid metabolism, and inflammation contribute to its pathogenesis. Scientists investigated whether a combination of FDA-approved therapies — atorvastatin, pioglitazone, and tofacitinib — targeting metabolic and inflammatory pathways would improve biomarkers of AD in an AD mouse model humanized APP and APOE genes.
- Treated mice showed better clearance of amyloid-beta, preserved lean mass, and had improved cognitive function compared to controls, with APOE4/4 female mice treated with all three drugs showing the strongest overall effects. This suggests therapies that target metabolic and inflammatory pathways could have therapeutic potential and emphasize the importance of accounting for sex in treatment experiments.
Altered Mitochondrial Function and Inflammation in Humanized APP/APOE Mouse Model of Alzheimer’s Disease Risk
Roberta Diaz Brinton, rbrinton@arizona.edu, Abstract PSTR437.06
- Disruption in cell metabolism and neuroinflammation are early drivers of AD. Using a mouse model with humanized APP/APOE, researchers examined the RNA sequences in the hippocampus — an area of the brain critical for memory — to determine how risk factors such as biological sex and genotype impacted these critical processes.
- Humanized APP/APOE4 mice exhibited significant changes in the expression of immune- and metabolic-related genes compared to humanized APP/APOE3. Female humanized APP/APOE4 mice had the most pronounced changes, including upregulated inflammatory gene activation and stress response pathways.
- This suggests an interplay between sex and the APOE high-risk genotype in AD pathogenesis.
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The Society for Neuroscience (SfN) is an organization of nearly 30,000 basic scientists and clinicians who study the brain and the nervous system.