Alzheimer’s disease may begin leaving detectable tissue loss in the brain up to a decade before memory problems appear, according to a Johns Hopkins University study published in NeuroImage Reports.
Researchers examined hundreds of brain scans and identified two regions that show deterioration earlier than the hippocampus. The findings were also presented at Neuroscience 2026, the annual meeting of the Society for Neuroscience.
“We have found that there are early changes in the brain manifesting the clinical biomarkers of atrophy as much as a decade before there are clinical symptoms,” said Michael Miller, biomedical engineer and senior author, EurekAlert! reported.
Entorhinal Cortex and Amygdala Deterioration
The research team analyzed magnetic resonance imaging and positron emission tomography scans from independent projects, including the Alzheimer’s Disease Neuroimaging Initiative. The data tracked individuals at various stages of the disease.
Results showed that the entorhinal cortex and the amygdala lose tissue earlier and show greater relative atrophy than the hippocampus during the early phase of the disease. The entorhinal cortex handles the retrieval of old memories, while the amygdala processes emotional memory.
“Our goal is to be able to treat individuals before the symptoms of Alzheimer’s disease develop so that they may delayed or even stopped,” said Marilyn Albert, co-author and director of the Johns Hopkins Alzheimer’s Disease Research Center.
Tau Protein Tangles Drive Gray Matter Shrinkage
Scientists linked the observed tissue loss to tau, a protein that forms abnormal tangles and interferes with nerve cell function in Alzheimer’s patients. PET imaging revealed that gray matter shrinkage overlaps with regions showing tau-related changes.
The researchers plan to investigate the molecular neighborhoods surrounding abnormal tau accumulation to better understand the biological processes driving tissue loss. “Our future work is to better show the molecular neighborhoods associated with these Tau protein changes as localized by these clinical biomarkers of atrophy,” biomedical engineer and senior author Michael Miller said.
“This could really play into better risk stratification for identifying who is going to have cognitive decline in the near future — and treating people earlier and earlier to hopefully slow the course of the disease,” said Meaghan Morris, co-author and neuropathologist.
ARC Scores Predict Cognitive Decline Patterns
In a related study published in Science Advances, Stanford Medicine researchers analyzed resting-state functional MRI scans to evaluate how brain regions work together. The team developed the Alzheimer’s Resilience–Vulnerability Connectome, or ARC, to measure brain connectivity.
Researchers calculated ARC scores for 1,315 adults without cognitive impairment, tracking participants for periods ranging from five to twelve years. Individuals with more Alzheimer’s-like connectivity patterns experienced faster cognitive decline and a higher risk of progressing to mild cognitive impairment.
“The ARC score summarizes whether an individual’s brain connectivity more closely resembles that of SuperAgers, who maintain exceptional memory into old age, or individuals with Alzheimer’s disease,” said Kanhao (Alex) Zhao, lead author and computational neuroscientist at Stanford Medicine, ScienceAlert reported.
Common Questions About Early Alzheimer’s Detection
Which brain regions show the earliest signs of Alzheimer’s deterioration?
The entorhinal cortex and the amygdala show tissue loss earlier and exhibit greater relative atrophy than the hippocampus during the early phase of the disease, according to the Johns Hopkins research team.
How far in advance can brain changes be detected?
Biomarkers of atrophy and functional connectivity patterns can manifest in the brain as much as a decade before clinical memory symptoms appear.
What is the Alzheimer’s Resilience–Vulnerability Connectome?
Developed by Stanford researchers, the ARC score evaluates resting-state functional MRI scans to determine whether an individual’s brain connectivity resembles that of SuperAgers or patients with Alzheimer’s disease.
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