Differential accumulation of secreted AβPP metabolites in ocular fluids

Annamalai Prakasam, Anusuya Muthuswamy, Zsolt Ablonczy, Nigel H. Greig, Abdul Fauq, Kosagisharaf Jagannatha Rao, Miguel A. Pappolla, Kumar Sambamurti

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Amyloid-β (Aβ) accumulates in several types of retinal degeneration and in Alzheimer's disease (AD), but its source has been unclear. We detected the neuronal 695 amino acid form of amyloid-β protein precursor (AβPP) in the normal retina and AβPP751 in the retinal pigment epithelium (RPE) and anterior eye tissues. Similar to the brain, α- and β-secretases cleaved AβPP to soluble derivatives (sAβPP) α or β and membrane-bound C-terminal fragments α or β in the retina and RPE. Levels of sAβPP were particularly high in the vitreous and low in aqueous humor revealing a molecular barrier for AβPP. In contrast, Aβ40 and Aβ42 levels were only 50% lower in the aqueous than the vitreous humor, indicating relatively barrier-free movement of Aβ. These studies demonstrated a relatively high yield of AβPP and Aβ in the ocular fluids, which may serve as a trackable marker for AD. In addition, failure of free clearance from the eye may trigger retina degeneration in a manner similar to Aβ-related neurodegeneration in AD.

Original languageEnglish (US)
Pages (from-to)1243-1253
Number of pages11
JournalJournal of Alzheimer's Disease
Volume20
Issue number4
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Age-related macular degeneration
  • Alzheimer's disease
  • amyloid-β protein precursor
  • aqueous humor
  • degeneration
  • eye vitreous humor
  • glaucoma
  • retina

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Prakasam, A., Muthuswamy, A., Ablonczy, Z., Greig, N. H., Fauq, A., Rao, K. J., Pappolla, M. A., & Sambamurti, K. (2010). Differential accumulation of secreted AβPP metabolites in ocular fluids. Journal of Alzheimer's Disease, 20(4), 1243-1253. https://doi.org/10.3233/JAD-2010-100210