In a quiet corner of the brain, two small structures near the hippocampus, the entorhinal cortex and the amygdala, appear to begin yielding tissue before the region long watched for signs of Alzheimer's gives way. Johns Hopkins researchers, drawing on hundreds of scans followed across years, found that this early erosion overlaps with the slow gathering of tau, a protein that normally steadies nerve cells but can tangle when it goes astray. The shift may unfold a decade before memory falters, offering a glimpse of a disease that has been quietly underway long before anyone notices it. For now,
Alzheimer's May Shrink Two Brain Regions Up to a Decade Before Memory Loss Appears
A five-to-ten-year window where the brain is changing before memory fails
Mark
Why does it matter that these two regions shrink before the hippocampus?
Mimi
Because the hippocampus is where doctors have traditionally looked. If the entorhinal cortex and amygdala change first, looking only at the hippocampus could mean missing the earliest signs.
Mark
What do those two regions actually do?
Mimi
The entorhinal cortex helps retrieve stored memories, and the amygdala handles emotional memory. Both sit near the hippocampus.
Luke
Before we get carried away, how strong is the decade claim?
Mimi
Miller framed it as at least a five-to-ten-year window of brain change before symptoms. The headline says up to a decade.
Luke
That's one researcher's characterization, and the study doesn't give us a test that predicts anything in an individual person. The source says plainly it hasn't established one.
Mark
What ties the shrinkage to Alzheimer's specifically?
Mimi
Tau. Gray matter loss overlapped with regions showing tau-related changes, using PET imaging and digital pathology.
Luke
Overlap is not the same as cause, though. The team says the next job is working out how tau changes contribute to tissue loss, so that's still open.
Mark
And the idea of scanning people in their 30s or 40s?
Mimi
That's a vision the researchers describe, contingent on imaging becoming cheaper and more accessible. It isn't a current practice.
O Pulso
- Two small brain regions may start shrinking up to a decade before memory loss, reshaping how the disease is understood.
- Doctors have long relied on the hippocampus, yet the earlier signal may lie elsewhere, raising urgency about where to look.
- Tau tangles appear to line up with the tissue loss, tying a visible change in scans to a molecular culprit.
- The findings are not yet a clinical test, so researchers are moving toward mapping molecular changes to guide future therapies.
In a quiet corner of the brain, two small structures near the hippocampus, the entorhinal cortex and the amygdala, appear to begin yielding tissue before the region long watched for signs of Alzheimer's gives way. Johns Hopkins researchers, drawing on hundreds of scans followed across years, found that this early erosion overlaps with the slow gathering of tau, a protein that normally steadies nerve cells but can tangle when it goes astray. The shift may unfold a decade before memory falters, offering a glimpse of a disease that has been quietly underway long before anyone notices it. For now, it is a clue to be studied, not a test to be trusted.
Researchers at Johns Hopkins have found that the entorhinal cortex and the amygdala begin losing tissue before the hippocampus does, and that this loss may start as much as a decade before memory trouble appears. The hippocampus is the structure doctors most often examine when they look for Alzheimer's, which makes this shift in attention meaningful.
The two regions sit close to the hippocampus. One helps retrieve memories already stored; the other shapes how emotional experiences are processed and remembered. Across hundreds of MRI and PET scans from two independent studies, following people with no symptoms, with cognitive impairment, and some who later died of the disease, the same early pattern appeared again and again.
The team also linked the shrinkage to tau, a protein that usually supports the internal structure of nerve cells but can build into tangles that disrupt healthy function. The areas losing gray matter overlapped with regions showing tau-related change. Senior author Michael Miller described a window of five to ten years before symptoms, and suggested that treatment begun years earlier might delay or even halt the disease.
The researchers caution that these findings are not yet a diagnostic tool. They point toward future screening, perhaps for people with family histories or other risks, but more work is needed. The next step is to examine these regions at a much finer scale, mapping the molecular changes around abnormal tau, with the hope that understanding them will open the way to new therapies.
Researchers at Johns Hopkins have found that two small brain regions begin to lose tissue before the hippocampus does, and that this shrinkage may start as much as a decade before memory loss shows up. The hippocampus is the structure doctors usually examine when they look for signs of Alzheimer's disease.
The two regions are the entorhinal cortex and the amygdala, both located near the hippocampus. The entorhinal cortex helps retrieve memories that have already been stored. The amygdala contributes to emotional memory, including how emotional experiences are processed and remembered. In the scans the team studied, both showed greater relative tissue loss than the hippocampus during the early stages of the disease.
To reach that conclusion, the team examined hundreds of MRI and PET brain scans drawn from two independent research projects: the Alzheimer's Disease Neuroimaging Initiative and the Biomarkers of Cognitive Decline Among Normal Individuals study. The scans followed people at different stages of Alzheimer's over time. Some had no symptoms, some had cognitive impairment, and some ultimately died of the disease. The same pattern appeared in both groups of data.
The researchers also connected the shrinkage to tau, a protein that normally helps maintain the internal structure of nerve cells. In Alzheimer's, tau can build up abnormally and form tangles that interfere with healthy brain function. Using PET imaging and digital pathology, the team found that areas of gray matter loss overlapped with regions showing tau-related changes. Gray matter holds large numbers of nerve cell bodies and is essential to processing information across the brain.
Michael Miller, a biomedical engineer and the study's senior author, described the timeline this way: the brain is changing over at least five to ten years before symptoms. He suggested that treatment started at the two-, three- or four-year point, rather than after about 15 years, when memory symptoms emerge, is the promise for people at risk. Marilyn Albert, a co-author who directs the Johns Hopkins Alzheimer's Disease Research Center, said the goal is to treat people before symptoms develop so the disease might be delayed or even stopped.
The team argues that measuring tissue loss in both regions, rather than leaning mainly on the hippocampus, could eventually sharpen predictions of who will develop cognitive decline. As imaging becomes cheaper and more accessible, researchers envision doctors checking these regions in people with a family history or other risk factors as early as their 30s or 40s. Co-author Meaghan Morris, a neuropathologist, said that as biomarkers and treatments become available, knowing who will decline will matter more, and could support better risk stratification and earlier treatment.
The work has clear limits. It identifies potential early biomarkers but does not establish a clinical test that can predict Alzheimer's years ahead, and more research is needed before doctors could use these changes diagnostically. The findings were published in NeuroImage Reports and are being presented at Neuroscience 2026, the Society for Neuroscience's annual meeting.
The next step is to look at these regions at a much smaller scale, mapping the molecular changes around abnormal tau and how they drive tissue loss. Miller said that once those molecular neighborhoods are better understood, therapies can be developed. That work, rather than a screening test, is what to watch for next.
Citações Notáveis
It's at least a 5-to-10-year play where your brain is changing.— Michael Miller, senior author
The goal is to treat people before Alzheimer's symptoms develop so the disease may be delayed or even stopped.— Marilyn Albert, co-author (paraphrased)
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