Changes in brain structure could occur seven years before Alzheimer's detection

Structural changes in the outer layer of the brain can be detected years before levels of beta-amyloid proteins reach high levels in brain scans, and this finding suggests that physical changes in brain tissue may be an earlier sign of Alzheimer's disease than previously thought.

Alzheimer’s disease is a progressive neurological disease that destroys memory and other important mental functions, and one of the main biological signs of the disease is the accumulation of beta-amyloid, a protein that sticks together to form plaques between nerve cells in the brain. Historically, the standard model of Alzheimer’s disease suggested that these amyloid plaques were formed first, which later cause brain wrinkles. A 2010 study suggested just such a timeline, arguing that amyloid accumulation was the very first event in the disease process, and brain volume loss occurs only as a later consequence.

Earlier studies have shown that elevated levels of beta-amyloid accelerate the loss of brain volume. For example, a 2024 study found that people with high levels of amyloid had brain volume shrinking faster, even before cognitive symptoms appeared. There are hints, however, that brain tissue may paradoxically swell and change long before amyloid scans become positive: a 2020 review notes that in the early stages of Alzheimer’s genetic disease, the outer layer of the brain temporarily thickens or swells before it begins to break down.

A new study directly tracks people over time to confirm that these changes in the cerebral cortex can be detected years before amyloid accumulation exceeds the detection threshold in brain scans. The cerebral cortex is the shrunken outer layer of the brain that plays an important role in memory, thinking and logical inference, and the thickness of this layer usually decreases with age — a process known as thinning of the cerebral cortex.

The study, led by James M. Rowe and Yunpeng Wang of the University of Oslo, aimed to find out whether changes in this thinning process occur before a person registers a positive test for beta-amyloid. To explore this chronology, the researchers analyzed data from three large long-term studies of cognitive aging, focusing on people who were cognitively healthy, meaning they showed no signs of dementia or cognitive impairment.

The researchers used magnetic resonance imaging, or MRI, which is a technique that uses magnetic fields to create detailed images of brain structure that allowed them to measure the thickness of the cortex over time, and used positron emission tomography, or PET scans, which use a low-radioactive indicator to determine the presence and number of beta-amyloid plaques in the brain.