Loss of apolipoprotein E receptor LR11 in Alzheimer disease
Abstract
Background Genetic, epidemiologic, and biochemical evidence suggests that apolipoprotein E, low-density lipoprotein receptors, and lipid metabolism play important roles in sporadic Alzheimer disease (AD). Objective To identify novel candidate genes associated with sporadic AD. Design We performed an unbiased microarray screen for genes differentially expressed in lymphoblasts of patients with sporadic AD and prioritized 1 gene product for further characterization in AD brain. Setting Emory University, Atlanta, Ga. Subjects Cell lines were used from 14 patients with AD and 9 normal human control subjects. Results Six genes were differentially expressed in lymphoblasts of 2 independent groups of patients with probable AD and autopsy-proven AD. We hypothesized that 1 of the genes, termed low-density lipoprotein receptor relative with 11 binding repeats (LR11) (reduced 1.8- and 2.5-fold in AD lymphoblasts vs controls), might be associated with sporadic AD on the basis of its function as neuronal apolipoprotein E receptor. We found dramatic and consistent loss of immunocytochemical staining for LR11 in histologically normal-appearing neurons in AD brains. This reduction of LR11 protein was confirmed by quantitative Western blotting (P =.01). Conclusions There is loss of the microarray-derived candidate, LR11, in neurons of AD brains. This study shows that microarray analysis of widely available lymphoblasts derived from patients with AD holds promise as a primary screen for candid…
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LR11/SorLA expression levels are lower in patients with sporadic AD.
“Its role in AD pathogenesis was initially suggested after the discovery of lower levels of LR11/SorLA expression in patients with sporadic AD (Scherzer et al., 2004)”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Scherzer et al., 2004
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- Authors
- Scherzer, C. R., Offe, K., Gearing, M., Rees, H. D., Fang, G., Heilman, C. J., Schaller, C., Bujo, H., Levey, A. I., & Lah, J. J.
- Affiliations
- Emory University (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2004-08-01
- Volume
- 61
- Issue
- 8
- Pages
- 1200-5
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2032822445
- Cited by
- 316
- References
- 1
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 13 · 2019: 9 · 2018: 14 · 2017: 16 · 2016: 24 · 2015: 13 · 2014: 19 · 2013: 11 · 2012: 27
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P30AG010130, U24AG021886)
- National Center for Research Resources (M01RR000039)
- 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
- Alzheimer's disease, LR11, apolipoprotein E receptor, candidate genes, gene expression profiling, lymphoblasts, neuronal loss, lipid metabolism
- MeSH terms
- Sortilin, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cell Line, Transformed, Female, Humans, Lymphocytes, Male, Membrane Glycoproteins, Middle Aged, Nerve Tissue Proteins, Receptors, LDL, Oligonucleotide Array Sequence Analysis, LDL-Receptor Related Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Membrane Transport Proteins, Adaptor Proteins, Vesicular Transport
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