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Neuronal LR11/sorLA expression is reduced in mild cognitive impairment
Kristen L Sager1, Joanne Wuu, Susan E Leurgans
1Center for Neurodegenerative Disease, Emory University, Atlanta, GA 30322, USA.
Annals of Neurology
|August 28, 2007
Summary
Reduced expression of the neuronal receptor LR11 (sorLA) is linked to Alzheimer's disease (AD) progression. Lower LR11 levels in mild cognitive impairment (MCI) correlate with cognitive decline, suggesting it may predict AD development.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- LR11 (sorLA) is a neuronal receptor involved in amyloid precursor protein processing and amyloidogenesis.
- Reduced LR11 expression is observed in Alzheimer's disease (AD) brains.
- Genetic variants in SORL1 are associated with late-onset AD risk.
Purpose of the Study:
- To investigate if LR11 expression is reduced early in the Alzheimer's disease process.
- To determine the association between neuronal LR11 protein levels and clinical/pathological changes in mild cognitive impairment (MCI), a prodromal AD state.
Main Methods:
- A novel quantitative immunohistochemical method was employed.
- LR11 levels were measured in brain tissue from individuals with no cognitive impairment, MCI, or AD.
- Data were sourced from the Rush University Religious Orders Study.
Main Results:
- LR11 levels in MCI subjects were intermediate between control and AD groups.
- MCI subjects with low LR11 expression exhibited significantly greater cognitive impairment.
- A significant correlation was found between cognitive performance and LR11 levels across all groups.
- No association was observed between LR11 levels and amyloid plaque or neurofibrillary tangle pathology.
Conclusions:
- Neuronal LR11 levels are decreased in prodromal AD (MCI).
- Reduced LR11 expression correlates with disease severity in MCI.
- LR11 levels may serve as a predictive biomarker for AD progression in a subset of MCI individuals.
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