Neuronal receptor linked to mild cognitive impairment & Alzheimer's

Mild cognitive impairment affects many cognitive functions, particularly memory. People with mild cognitive impairment are 3-4 times more likely to develop Alzheimer's Disease; hence, it is regarded as a transition stage between normal age-related cognitive decline and Alzheimer's Disease.

Researchers Emory University School of Medicine and Rush University Medical Center in Chicago now report that reduced levels of a receptor found in nerve cells is associated with the onset of mild cognitive impairment. A strong correlation between receptor levels and cognitive performance was also found. The new findings suggest that levels of the receptor levels could be an indication of diseases severity. 

The receptor in question is lipoprotein receptor 11 (LR11), which binds to apolipoprotein E and interacts with amyloid precursor protein (APP), both of which are associated with Alzheimer's. People who inherit two copies of a particluar variation of the apolipoprotein gene have a higher risk of developing Alzheimer's after 65 years of age; sequential actions of enzymes on APP lead to the  formation of amyloid-beta, the insoluble protein which aggregates to form the plaques that are a pathological hallmark of Alzheimer's.

Previous work had already implicated LR11 in Alzheimer's. The receptor is known to regulate amyloidogenesis, the process by which amyloid-beta accumulates to form plaques in the brains of Alzheimer's patients, and its expression levels are known to be reduced by up to 25% in patients' brains.

Sager and her colleagues therefore investigated levels of LR11 expression in brain tissue collected from people who had been diagnosed before their death with either mild cognitive impairment or Alzheimer's, Some of the tissue samples came from people who had no form of ognitive impairment.

A   strong correlation between LR11expression levels and the extent of cognitive impairment. Tissue samples from patients who had been diagnosed with Alzheimer's had the lowest expression levels, while samples from patients without cognitive impairment had normal expression levels. Tissue from patients who had been diagnosed with mild cognitive impairment had intermediate levels of LR11 expression.

Even within those three categories of samples, there were differences in LR11 expression levels. All the patients from whom tissues were collected had undergone cognitive performance testing before their deaths. The researchers' analyses showed a correlation between performance on tests of cognitive ability and LR11 expression levels. For example, in all the patients who had been diagnosed with mild cognitive impairment, those who had a better cognitive performance had higher levels of LR11 in their brain tissue.

The correlation between LR11 expression levels and cognitive performance was very strong - it was also found in the group that had not been diagnosed with mild cognitive impairment. This suggests that the level of LR11 expression is somehow related to cognitive ability.

This study provides further evidence that LR11 levels are linked to cognitive impairment and to development of Alzheimer's Disease. Because many people with mild cognitive impairment are in the early clinical stages of Alzheimer's Disease, the level of LR11 expression could be an indicator of both the likelihood of developing Alzheimer's and the severity of the disease.

Reference:

Sager, K. L., et al. (2007). Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. Ann. Neurol. doi: 10.1002/ana.21151. [Abstract]