title: Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease.
abstract: BACKGROUND
  Pathological hallmarks of Alzheimer's disease include cerebral beta-amyloid (Abeta) deposition, amyloid accumulation, and neuritic plaque formation. We aimed to investigate the hypothesis that molecular pathological findings associated with Alzheimer's disease overlap in the lens and brain.
  
  
  METHODS
  We obtained postmortem specimens of eyes and brain from nine individuals with Alzheimer's disease and eight controls without the disorder, and samples of primary aqueous humour from three people without the disorder who were undergoing cataract surgery. Dissected lenses were analysed by slit-lamp stereophotomicroscopy, western blot, tryptic-digest/mass spectrometry electrospray ionisation, and anti-Abeta surface-enhanced laser desorption ionisation (SELDI) mass spectrometry, immunohistochemistry, and immunogold electron microscopy. Aqueous humour was analysed by anti-Abeta SELDI mass spectrometry. We did binding and aggregation studies to investigate Abeta-lens protein interactions.
  
  
  RESULTS
  We identified Abeta1-40 and Abeta1-42 in lenses from people with and without Alzheimer's disease at concentrations comparable with brain, and Abeta1-40 in primary aqueous humour at concentrations comparable with cerebrospinal fluid. Abeta accumulated in lenses from individuals with Alzheimer's disease as electron-dense deposits located exclusively in the cytoplasm of supranuclear/deep cortical lens fibre cells (n=4). We consistently saw equatorial supranuclear cataracts in lenses from people with Alzheimer's disease (n=9) but not in controls (n=8). These supranuclear cataracts colocalised with enhanced Abeta immunoreactivity and birefringent Congo Red staining. Synthetic Abeta bound alphaB-crystallin, an abundant cytosolic lens protein. Abeta promoted lens protein aggregation that showed protofibrils, birefringent Congo Red staining, and Abeta/alphaB-crystallin coimmunoreactivity.
  
  
  CONCLUSIONS
  Abeta is present in the cytosol of lens fibre cells of people with Alzheimer's disease. Lens Abeta might promote regionally-specific lens protein aggregation, extracerebral amyloid formation, and supranuclear cataracts.
authors.affiliation: Laboratory for Oxidation Biology, Massachusetts General Hospital, Charlestown, MA 02129-4404, USA.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.forename: Julien A
authors.initials: JA
authors.lastname: Muffat
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.forename: Robert D
authors.initials: RD
authors.lastname: Moir
authors.forename: Maria H
authors.initials: MH
authors.lastname: Ericsson
authors.forename: Xudong
authors.initials: X
authors.lastname: Huang
authors.forename: Christine
authors.initials: C
authors.lastname: Mavros
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Coccia
authors.forename: Kyle Y
authors.initials: KY
authors.lastname: Faget
authors.forename: Karlotta A
authors.initials: KA
authors.lastname: Fitch
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Leo T
authors.initials: LT
authors.lastname: Chylack
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D001082:Aqueous Humor / Q000737:chemistry*; D002386:Cataract / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D012016:Reference Values
chemical_list: D016229:Amyloid beta-Peptides