A new study led by University of California, Irvine researchers indicates that Alzheimer’s disease can manifest with similar brain damage and memory loss across individuals, even when different biological processes are at work. The findings, published on August 7, 2026, in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, suggest that Alzheimer’s is not uniformly driven by the same biological mechanism in every person.
Researchers identified two distinct patterns involving inflammation within the brain. One pattern was associated with damage to the brain’s small blood vessels, a marker known as white matter hyperintensities. This pattern correlated with higher levels of YKL-40, a protein found in blood that signals the activity of brain support cells responding to injury. The other inflammatory pattern was linked to the buildup of amyloid beta, a protein widely recognized as a hallmark of Alzheimer’s disease. This pattern correlated with elevated levels of glial fibrillary acidic protein (GFAP) in the blood, another marker associated with brain support cell activity.
Despite these differences in underlying inflammatory markers, both patterns were connected to common downstream effects. They were associated with higher levels of phosphorylated tau 217 (p-tau217), a blood marker used to detect abnormal changes involving tau, another protein central to Alzheimer’s. Both inflammatory pathways also connected to shrinkage in brain regions critical for memory, specifically the medial temporal lobe and the hippocampus. Participants showing a smaller hippocampal volume subsequently performed worse on memory tests that assessed their ability to retain information after new material was presented.
The research was conducted by studying 126 adults, aged 60 and older, who did not exhibit mild cognitive impairment or dementia. These participants were enrolled in the NIH-funded Biomarker Exploration in Aging, Cognition, and Neurodegeneration, or BEACoN, study, led by Michael A. Yassa. The research team utilized a combination of blood tests, magnetic resonance imaging (MRI), amyloid PET brain scans, and memory assessments. Scientists then applied a statistical model to understand the connections between these various markers and the resulting memory loss.
These findings carry potential clinical implications, suggesting that future therapies could be more precisely targeted. The study offers one explanation for the limited success of some Alzheimer’s clinical trials to date. According to senior author Michael A. Yassa, PhD, professor and James L. McGaugh Endowed Chair in Neurobiology and Behavior and director of UC Irvine’s Center for the Neurobiology of Learning & Memory, "The biology is much messier than that." Dr. Yassa indicated that diverse biological issues might push the brain toward a similar damaged state, emphasizing that for treatment, the key may be understanding which processes are causing the most harm in each individual and how these processes interact.
First author Batool Rizvi, PhD, who conducted the work as a graduate student with Yassa, noted that the two blood markers signaled different processes that ultimately connect to the visible signs of Alzheimer’s. Dr. Rizvi stated that their results suggest that "inflammation in Alzheimer’s is not one single process," and that different inflammatory mechanisms may act in parallel to converge on the same outcome of cell loss.
The study supports a broader perspective on Alzheimer’s disease, previously articulated by Dr. Yassa in a 2025 essay titled 'Everything, everywhere, all at once: Inside the chaos of Alzheimer’s disease,' published in The Transmitter. In that essay, Dr. Yassa proposed that Alzheimer’s symptoms may appear similar because several biological problems — including amyloid buildup, inflammation, blood vessel injury, issues with glucose use, or excessive brain activity — can eventually lead to the same symptoms. These processes can also interact, creating a damaged and unstable brain state that persists even after initial triggers are reduced. Dr. Yassa summarized the disease as 'less like a single chain of events and more like several roads leading to the same place,' highlighting increased opportunities for treatment if main biological drivers in each person are identified.
The researchers cautioned that the study offers a snapshot in time, meaning it cannot determine the sequence of changes or establish direct cause-and-effect relationships. The participants were cognitively unimpaired, and some blood measurements were available only for a subset of the study group. The sample was also predominantly White, which may limit the broad applicability of the results. Future research will need to involve larger, more diverse groups of people, followed over extended periods. Future studies should also explore whether these identified patterns predict memory decline, how they evolve as Alzheimer’s progresses, and their potential use in selecting and informing treatments.
This study received support from the National Institute on Aging grant R01AG053555.
