Irvine, Calif. — March 11, 2025 — A new study from researchers at the University of California, Irvine’s Center for the Neurobiology of Learning and Memory (CNLM) has uncovered a critical link between early Alzheimer’s disease (AD) pathology and a specific type of memory impairment that occurs decades before clinical symptoms appear.

The study, led by senior author Dr. Jenna Adams and first author MD/PhD student Casey Vanderlip in the laboratory of CNLM Director Dr. Michael Yassa, reveals that early buildup of amyloid-beta (Aβ) in specific areas of the brain selectively affects how we remember the timing of events—a cognitive function supported by brain regions that are among the first affected in Alzheimer’s disease.

A New Clue for Early Alzheimer’s Detection

Alzheimer’s disease begins with the accumulation of Aβ in the brain, a process that can start 20 to 30 years before noticeable cognitive decline. However, until now, it was unclear whether this early Aβ buildup was linked to subtle memory deficits.

The study, published in the Journal of Neuroscience, tested 108 cognitively unimpaired older adults using cutting-edge brain imaging techniques and specialized memory tasks as part of the NIH-funded BEACoN Project. The researchers found that while normal aging affects memory for objects and spatial locations, elevated Aβ levels were specifically associated with impairments in remembering when events occurred—a function known as temporal mnemonic discrimination.

“We were excited to observe that even in individuals already showing elevated amyloid-beta levels, higher Aβ in brain regions vulnerable to Alzheimer’s disease was linked to worse performance in temporal discrimination tasks,” said Dr. Jenna Adams. “This highlights the sensitivity of this task in detecting the subtle effects of Aβ progression on memory, long before outward signs of cognitive impairment appear.”

Why Memory for Time Matters

Memory is often thought of in terms of recalling what happened or where it happened, but our ability to remember when events occurred is equally important. This skill, called temporal mnemonic discrimination, relies on circuits in the frontal and temporal lobes—regions where Aβ accumulates in early Alzheimer’s disease. The study found that Aβ deposition in the medial orbitofrontal cortex and inferior temporal cortex was strongly linked to deficits in remembering the order of events. 

“We don’t just remember what happened—we also remember when things happened,” explained Casey Vanderlip. “This ability helps us make sense of our daily lives, and our study shows that it’s one of the first cognitive functions affected by Alzheimer’s. This makes it a promising target for early detection of the disease.”

Potential Impact on Alzheimer’s Diagnosis and Treatment

These results have significant implications for early detection and clinical trials. Currently, many Alzheimer’s screening tools focus on memory for words or pictures, but this study suggests that including tasks that assess memory for time could improve early diagnosis.

Furthermore, as new drugs targeting Aβ continue to be developed, tracking changes in temporal memory could help measure whether these treatments are effective in slowing Alzheimer’s progression.

“Our hope is that these findings will lead to new clinical assessments that help identify at-risk individuals sooner and improve treatment outcomes,” said Yassa, Professor and James L. McGaugh Endowed Chair in Neurobiology and Principal Investigator of the BEACoN project.

What’s Next?

The research team plans to expand their study to longitudinal research, tracking whether individuals with temporal memory deficits are more likely to develop Alzheimer’s symptoms over time. They also aim to investigate the role of tau pathology, another key Alzheimer’s-related brain change, in combination with Aβ.

By deepening our understanding of how Alzheimer’s develops before symptoms appear, the BEACoN team is paving the way for earlier detection and more effective interventions—a crucial step toward changing the course of the disease.

Read the article at: https://www.jneurosci.org/content/45/10/e1605242025

Learn more about the Yassa Translational Neurobiology Lab at yassalab.org

Learn more about the Center for the Neurobiology of Learning and Memory at cnlm.uci.edu