title: Neuronal LR11/sorLA expression is reduced in mild cognitive impairment.
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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Neurodegenerative Disease, Emory University, Atlanta, GA 30322, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Sager
authors.forename: Joanne
authors.initials: J
authors.lastname: Wuu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Leurgans
authors.forename: Howard D
authors.initials: HD
authors.lastname: Rees
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
authors.forename: James J
authors.initials: JJ
authors.lastname: Lah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D026502:LDL-Receptor Related Proteins / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000473:pathology; D012720:Severity of Illness Index; D013194:Staining and Labeling; D024801:Tauopathies / Q000473:pathology
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human