Neuronal LR11/sorLA expression is reduced in mild cognitive impairment
Open accessAbstract
Objective: LR11 (aka sorLA) is a multifunctional neuronal receptor that binds apolipoprotein E and interacts with amyloid precursor protein to regulate amyloidogenesis. Reduced expression of LR11, as occurs in the brains of individuals with Alzheimer's disease (AD), increases amyloidogenesis, and variants in the gene that encodes LR11, SORL1, have recently been linked to risk for late‐onset AD. In this study, we sought to determine whether reduced expression of LR11 occurs early in the disease process and whether protein levels in cortical neurons are associated with clinical and pathological changes in mild cognitive impairment (MCI), a condition that may represent prodromal AD. Methods: A novel quantitative immunohistochemical approach was used to measure LR11 levels in brain tissue collected from subjects diagnosed antemortem with either no cognitive impairment, MCI, or AD from the Rush University Religious Orders Study. Results: LR11 levels in MCI were intermediate between no cognitive impairment and AD. LR11 expression was heterogeneous in MCI, forming low‐ and high‐level LR11 subgroups. MCI subjects with low LR11 were significantly more cognitively impaired than the high LR11 subjects. We also found a significant correlation between cognitive performance and LR11 levels across all clinical groups examined. There was no association between LR11 and plaque and tangle pathology. Interpretation: Neuronal LR11 levels are reduced in prodomal AD. The correlation between LR11 expression and cognitive performance indicates that reduced LR11 levels reflect disease severity and may predict progression to AD in a subgroup of individuals with MCI. Ann Neurol 2007
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LR11/SorLA expression levels are lower in patients with mild cognitive impairment.
“and mild cognitive impairment (Sager et al., 2007).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Sager et al., 2007
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- Authors
- Sager, K. L., Wuu, J., Leurgans, S. E., Rees, H. D., Gearing, M., Mufson, E. J., Levey, A. I., & Lah, J. J.
- Affiliations
- Emory University (US)
- Rush University Medical Center (US)
- Corresponding author
- Lah, James J.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2007-08-24
- Volume
- 62
- Issue
- 6
- Pages
- 640-647
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2669325
- OpenAlex
- W2016590297
- Cited by
- 96
- References
- 5
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 11 · 2013: 6 · 2012: 7
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG024214, P01AG014449, P30AG010161, R01AG043375, P50AG025688)
- National Institute of Neurological Disorders and Stroke (F31NS054436)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- LR11, SorLA, SORL1, mild cognitive impairment, Alzheimer's disease, prodromal Alzheimer's disease, amyloid precursor protein, apolipoprotein E, amyloidogenesis, cortical neurons, cognitive performance, amyloid plaques, neurofibrillary tangles, disease progression prediction
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Female, Humans, Immunohistochemistry, Male, Neurons, Severity of Illness Index, Staining and Labeling, Tauopathies, LDL-Receptor Related Proteins, Membrane Transport Proteins, Plaque, Amyloid
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