Neuronal LR11/SorLA expression is reduced in mild cognitive impairment

Kristen L. Sager, Joanne Wuu, Susan E. Leurgans, Howard D. Rees, Maria Gearing, Elliott J. Mufson, Allan I. Levey, James J. Lah

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 LRU, 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 measute 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.

Original languageEnglish
Pages (from-to)640-647
Number of pages8
JournalAnnals of Neurology
Volume62
Issue number6
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

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Alzheimer Disease
Low Density Lipoprotein Receptor-Related Protein-1
Cognitive Dysfunction
Amyloid beta-Protein Precursor
Brain
Pathology
Neurons
Genes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sager, K. L., Wuu, J., Leurgans, S. E., Rees, H. D., Gearing, M., Mufson, E. J., ... Lah, J. J. (2007). Neuronal LR11/SorLA expression is reduced in mild cognitive impairment. Annals of Neurology, 62(6), 640-647. https://doi.org/10.1002/ana.21190

Neuronal LR11/SorLA expression is reduced in mild cognitive impairment. / Sager, Kristen L.; Wuu, Joanne; Leurgans, Susan E.; Rees, Howard D.; Gearing, Maria; Mufson, Elliott J.; Levey, Allan I.; Lah, James J.

In: Annals of Neurology, Vol. 62, No. 6, 01.12.2007, p. 640-647.

Research output: Contribution to journalArticle

Sager, KL, Wuu, J, Leurgans, SE, Rees, HD, Gearing, M, Mufson, EJ, Levey, AI & Lah, JJ 2007, 'Neuronal LR11/SorLA expression is reduced in mild cognitive impairment', Annals of Neurology, vol. 62, no. 6, pp. 640-647. https://doi.org/10.1002/ana.21190
Sager KL, Wuu J, Leurgans SE, Rees HD, Gearing M, Mufson EJ et al. Neuronal LR11/SorLA expression is reduced in mild cognitive impairment. Annals of Neurology. 2007 Dec 1;62(6):640-647. https://doi.org/10.1002/ana.21190
Sager, Kristen L. ; Wuu, Joanne ; Leurgans, Susan E. ; Rees, Howard D. ; Gearing, Maria ; Mufson, Elliott J. ; Levey, Allan I. ; Lah, James J. / Neuronal LR11/SorLA expression is reduced in mild cognitive impairment. In: Annals of Neurology. 2007 ; Vol. 62, No. 6. pp. 640-647.
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