Differential Accumulation of Secreted AβPP Metabolites in Ocular Fluids¹

Article type: Research Article

Authors: Prakasam, Annamalai^a | Muthuswamy, Anusuya^a | Ablonczy, Zsolt^b | Greig, Nigel H.^c | Fauq, Abdul^d | Rao, Kosagisharaf Jagannatha^a | Pappolla, Miguel A.^a | Sambamurti, Kumar^{a; *}

Affiliations: [a] Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA | [b] Department of Ophthalmology, Medical University of South Carolina, Storm Eye Institute, Charleston, SC, USA | [c] Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA | [d] Department of Neurosciences, Mayo Clinic, Jacksonville, FL, USA

Correspondence: [*] Correspondence to: Kumar Sambamurti, Ph.D., Professor, Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA. Fax: +1 843 792 1066; E-mail: [email protected].

Note: [1] This article received a correction notice (Erratum) with the reference: 10.3233/JAD-239014, available at http://doi.org/10.3233/JAD-239014.

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, a- and β-secretases cleaved AβPP to soluble derivatives (sAβPP) a or β and membrane-bound C-terminal fragments a 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.

Keywords: Age-related macular degeneration, Alzheimer’s disease, amyloid-β protein precursor, aqueous humor, degeneration, eye vitreous humor, glaucoma, retina

DOI: 10.3233/JAD-2010-100210

Journal: Journal of Alzheimer's Disease, vol. 20, no. 4, pp. 1243-1253, 2010