Researchers have identified a potential new biological marker that could help detect Alzheimer’s disease (AD) at a much earlier stage than currently possible, by focusing on how the brain processes smell and memory.

Axar.az informs that Alzheimer’s disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline, driven largely by the accumulation of amyloid and tau proteins that damage neurons and disrupt brain connectivity. While symptoms typically emerge later in life, scientists have long suspected that subtle neurological changes begin years earlier.

A new study published in Molecular Psychiatry has now uncovered that disruptions in specific brain circuits involved in olfactory processing may serve as an early indicator of the disease.

Olfactory-Memory Circuit Disruption Found Early

Researchers from Shenzhen MSU-BIT University, Chongqing Medical University Children’s Hospital, and collaborating institutions investigated how Alzheimer’s affects brain networks responsible for smell and memory.

Using functional magnetic resonance imaging (fMRI), the team found that connectivity between the piriform cortex (PCx)—a region responsible for processing smell—and the infralimbic (IL) cortex, which is involved in memory and decision-making, was significantly impaired during the early mild cognitive impairment (MCI) stage of Alzheimer’s.

According to the researchers, this disruption occurs before the onset of major cognitive decline, suggesting it could serve as an early biological signal of disease progression.

Cellular-Level Mechanisms Identified

To further understand the underlying biological processes, the scientists conducted experiments using genetically engineered 5xFAD mice, a widely used model of Alzheimer’s disease.

Through optogenetic stimulation and single-cell RNA sequencing, the researchers observed that activating specific PCx neurons projecting to the IL cortex could restore olfactory memory performance in the mice.

The analysis also revealed elevated glutamate-related activity and impaired synaptic function within these neural circuits. In particular, dysfunction of AMPA-type glutamate receptors was found to weaken synaptic communication between brain regions critical for smell and memory.

Potential for Early Diagnosis and Treatment

The study suggests that Alzheimer’s disease may begin affecting brain function earlier than previously understood, particularly within neural circuits linked to olfaction.

By identifying measurable changes in PCx–IL connectivity, the findings open the door to potential early diagnostic tools based on brain imaging or olfactory testing. They may also inform future therapeutic strategies aimed at restoring synaptic function before severe cognitive decline occurs.

Researchers caution that further studies in human patients are needed to validate these findings and determine how they can be translated into clinical practice.

Still, the discovery strengthens growing evidence that loss of smell is not merely a symptom of Alzheimer’s disease, but may be a key early biomarker of its development.