Ab in Lens in Down Syndrome Figure 3. Alzheimer’s disease amyloid-b (Ab) pathology in Down syndrome lens. (A) Histological section of a human lens obtained from a 21-year-old male subject with Down syndrome. Hematoxylin and eosin. (B) Schematic diagram identifying anatomical regions of the human lens (adapted from Histology of the Human Eye: An Atlas and Textbook [52]). (C) Archival rendering of classical coronary cerulean ‘‘flake’’ arcuate cataracts in a 40-year-old male with presumptive Down syndrome (from Lowe, 1949 [23]). This historical folio drawing illustrates the mature Down syndrome supranuclear cataract phenotype with dominant subequatorial localization and anteroposterior extension. (D-F) Congo red amyloid histochemical analysis of lenses from a 21-year-old male with Down syndrome and age-matched normal male control. (D) Congophilia in the cortex and supranuclear subregion of the lens from a 21-year-old male with Down syndrome. (E) Intense co-localizing apple-green birefringence in the corresponding cortical and supranuclear subregions of the same Congo red-stained Down syndrome lens imaged with cross-polarized illumination. (F) Amyloid histochemical analysis of a lens from a 21-year-old normal control subject did not demonstrate Congophilia nor classical apple-green birefringence under identical cross-polarized illumination. (G) Ab immunoreactivity in the epithelium, deep cortex, and supranuclear regions in a lens from a 22-year-old male with Down syndrome. Inset, magnified detail of the anterior lens (box). Cap, capsule; epi, epithelium; cor, cortex; snc, supranucleus; nuc, nucleus. (H) Confirmation of anti-Ab antibody specificity in the same Down syndrome lens by immunodepletion of the detection antibody with synthetic human Ab. Adjacent section of the same Down syndrome lens in Fig. 3G (I) Absence of Ab immunoreactivity in the lens of a normal 22-year-old male control subject. (J) Anti-Ab immunogold electron microscopic analysis of lens from a 58-year-old male with Down syndrome. Heterogeneously distributed anti-Ab immunoreactive protein aggregates of dimensions ,5–200 nm localize heterogeneously within the lens fiber cell cytoplasm. Ab immunoreactivity was not detected at the plasmalemma. Boxed region denotes magnified area shown in Fig. 3k. Scale PLoS ONE | www.plosone.org 6 May 2010 | Volume 5 | Issue 5 | e10659