A new study by Emory researchers finds that an early decrease of a neurological receptor may be a factor in the development of Alzheimer’s disease.

Decreased levels of the low-density lipoprotein receptor-related protein 11, or LR11, is linked to the severity of Mild Cognitive Impairment (MCI), a condition that can progress to Alzheimer’s disease (AD), according to a study by Associate Professor of Neurology James Lah and graduate student Kristen Sager.

The study will be published in the Annals of Neurology next month.

The brains of patients diagnosed with MCI or Alzheimer’s disease were compared to patients with normal cognitive functions. LR11 levels were decreased in both MCI and AD brains. The level of decrease LR11 also correlated with the severity of MCI, suggesting that LR11 has an early role in mental deterioration.

This study confirms previous findings that LR11 levels are lower in brains with AD.

LR11 is a receptor that acts as a “cellular traffic cop,” Lah said. Importantly for Alzheimer’s disease, LR11 also controls the levels of a small protein fragment called amyloid-beta.

The plaques amyloid-beta can form in the brain are a hallmark of Alzheimer’s disease. The study suggests that without LR11, plaque formation will accelerate, leading to AD.

MCI is a condition characterized by a decrease in normal brain function in key areas such as learning and memory. But individuals with MCI are able to function normally in their daily activities.

“MCI does not necessarily condemn a person to Alzheimer’s disease,” Lah said. “There is a 10 to 15 percent progression to AD after 1 year ... but there is some reversion to the normal state.”

Data for the study were gathered from participants in Rush University’s (Ill.) Religious Orders study. Participants in the study included nuns and priests who agreed to medical evaluations throughout their lifetimes and donated their organs upon death.

According to Lah, they were ideal subjects because they entered the study young, followed similar diets and abstained from harmful substances like drugs and alcohol.

“When we looked at everything that was already known about LR11 and Alzheimer’s disease, it seemed obvious that the loss of LR11 happens very early in the disease process,” said Sager. “In order to properly test this hypothesis, though, we needed to find a population of individuals who didn’t have Alzheimer’s yet, but who would get it eventually. And for us, studying LR11 in the brains of individuals with Mild Cognitive Impairment was the ideal solution.”

The researchers are hopeful that LR11 levels can be used as a “biomarker for cognitive decline,” Lah said. This would allow doctors to relate patients’ symptoms to a specific pathway in the brain.

“When it comes down to it, that’s what really matters to most people — how the pathology that we study in the brain directly relates to the symptoms that they experience,” Sager said.

The new findings may open the door for developing treatments that intervene and compensate for the loss of the receptor before AD develops.

— Contact Brett Israel at bisrael@emory.edu.