Differential accumulation of secreted AβPP metabolites in ocular fluids

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

Fingerprint

Amyloid beta-Protein Precursor
Retina
Alzheimer Disease
Retinal Pigment Epithelium
Aqueous Humor
Pigment Epithelium of Eye
Vitreous Body
Amyloid Precursor Protein Secretases
Retinal Degeneration
Staphylococcal Protein A
Amyloid
Amino Acids
Membranes
Brain

Keywords

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

ASJC Scopus subject areas

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

Cite this

Prakasam, A., Muthuswamy, A., Ablonczy, Z., Greig, N. H., Fauq, A., Rao, K. J., ... 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

Differential accumulation of secreted AβPP metabolites in ocular fluids. / Prakasam, Annamalai; Muthuswamy, Anusuya; Ablonczy, Zsolt; Greig, Nigel H.; Fauq, Abdul; Rao, Kosagisharaf Jagannatha; Pappolla, Miguel; Sambamurti, Kumar.

In: Journal of Alzheimer's Disease, Vol. 20, No. 4, 2010, p. 1243-1253.

Research output: Contribution to journalArticle

Prakasam, A, Muthuswamy, A, Ablonczy, Z, Greig, NH, Fauq, A, Rao, KJ, Pappolla, M & Sambamurti, K 2010, 'Differential accumulation of secreted AβPP metabolites in ocular fluids', Journal of Alzheimer's Disease, vol. 20, no. 4, pp. 1243-1253. https://doi.org/10.3233/JAD-2010-100210
Prakasam A, Muthuswamy A, Ablonczy Z, Greig NH, Fauq A, Rao KJ et al. Differential accumulation of secreted AβPP metabolites in ocular fluids. Journal of Alzheimer's Disease. 2010;20(4):1243-1253. https://doi.org/10.3233/JAD-2010-100210
Prakasam, Annamalai ; Muthuswamy, Anusuya ; Ablonczy, Zsolt ; Greig, Nigel H. ; Fauq, Abdul ; Rao, Kosagisharaf Jagannatha ; Pappolla, Miguel ; Sambamurti, Kumar. / Differential accumulation of secreted AβPP metabolites in ocular fluids. In: Journal of Alzheimer's Disease. 2010 ; Vol. 20, No. 4. pp. 1243-1253.
@article{3f8ae092dff745b3afe9ab6d124e5931,
title = "Differential accumulation of secreted AβPP metabolites in ocular fluids",
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.",
keywords = "Age-related macular degeneration, Alzheimer's disease, amyloid-β protein precursor, aqueous humor, degeneration, eye vitreous humor, glaucoma, retina",
author = "Annamalai Prakasam and Anusuya Muthuswamy and Zsolt Ablonczy and Greig, {Nigel H.} and Abdul Fauq and Rao, {Kosagisharaf Jagannatha} and Miguel Pappolla and Kumar Sambamurti",
year = "2010",
doi = "10.3233/JAD-2010-100210",
language = "English (US)",
volume = "20",
pages = "1243--1253",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "4",

}

TY - JOUR

T1 - Differential accumulation of secreted AβPP metabolites in ocular fluids

AU - Prakasam, Annamalai

AU - Muthuswamy, Anusuya

AU - Ablonczy, Zsolt

AU - Greig, Nigel H.

AU - Fauq, Abdul

AU - Rao, Kosagisharaf Jagannatha

AU - Pappolla, Miguel

AU - Sambamurti, Kumar

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Age-related macular degeneration

KW - Alzheimer's disease

KW - amyloid-β protein precursor

KW - aqueous humor

KW - degeneration

KW - eye vitreous humor

KW - glaucoma

KW - retina

UR - http://www.scopus.com/inward/record.url?scp=77954551693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954551693&partnerID=8YFLogxK

U2 - 10.3233/JAD-2010-100210

DO - 10.3233/JAD-2010-100210

M3 - Article

VL - 20

SP - 1243

EP - 1253

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -