Cellular and Molecular Life Sciences

, Volume 73, Issue 22, pp 4279–4297 | Cite as

One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

  • Vivek Gupta
  • Veer B. Gupta
  • Nitin Chitranshi
  • Sumudu Gangoda
  • Roshana Vander Wall
  • Mojdeh Abbasi
  • Mojtaba Golzan
  • Yogita Dheer
  • Tejal Shah
  • Alberto Avolio
  • Roger Chung
  • Ralph Martins
  • Stuart Graham
Review

Abstract

Accumulation of amyloid β (Aβ) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer’s disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of Aβ accumulation as well as its in vivo roles remains elusive; nonetheless, the majority of the efforts to address pathological mechanisms for therapeutic development are focused towards moderating Aβ accumulation in the brain. More recently, Aβ deposition has been identified in the eye and is linked with distinct age-related diseases including age-related macular degeneration, glaucoma as well as AD. Awareness of the Aβ accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for Aβ and the potential to use retina as a model for brain related neurodegenerative disorders. Here, we present an integrated view of current understanding of the retinal Aβ deposition discussing the accumulation mechanisms, anticipated impacts and outlining ameliorative approaches that can be extrapolated to the retina for potential therapeutic benefits. Further longitudinal investigations in humans and animal models will determine retinal Aβ association as a potential pathognomonic, diagnostic or prognostic biomarker.

Keywords

Neurotrophic factors Mitochondrial impairment Protein aggregation Inflammation Oxidative stress Electroretinogram Optical coherence tomography Metal ions Vascular dysfunction 

Abbreviations

AD

Alzheimer’s disease

AMD

Age-related macular degeneration

Amyloid beta

RGC

Retinal ganglion cell

APP

Amyloid precursor protein

RNFL

Retinal nerve fibre layer

PERG

Pattern electroretinogram

VEP

Visual evoked potential

OCT

Optical coherence tomography

RPE

Retinal pigment epithelium

BrM

Bruch’s membrane

IOP

Intra ocular pressure

BDNF

Brain derived neurotrophic factor

CNTF

Ciliary neurotrophic factor

GDNF

Glial derived neurotrophic factor

Arc

Activity regulated cytoskeleton-associated protein

BACE

β Secretase

ACE

Angiotensin converting enzyme

AGE

Advanced glycation end product

VEGF

Vascular endothelial growth factor

INL

Inner nuclear layer

ROS

Reactive oxygen species

ONH

Optic nerve head

NSAID

Non-steroidal anti-inflammatory drugs

HRT

Hormone replacement therapy

LH

Luteinizing hormone

GRH

Gonadotrophin releasing hormone

SOD

Superoxide dismutase

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Vivek Gupta
    • 1
  • Veer B. Gupta
    • 2
  • Nitin Chitranshi
    • 1
  • Sumudu Gangoda
    • 1
  • Roshana Vander Wall
    • 1
  • Mojdeh Abbasi
    • 1
  • Mojtaba Golzan
    • 1
  • Yogita Dheer
    • 1
  • Tejal Shah
    • 2
  • Alberto Avolio
    • 1
  • Roger Chung
    • 1
  • Ralph Martins
    • 2
  • Stuart Graham
    • 1
    • 3
  1. 1.Faculty of Medicine and Health SciencesMacquarie UniversitySydneyAustralia
  2. 2.School of Medical SciencesEdith Cowan UniversityPerthAustralia
  3. 3.Save Sight InstituteSydney UniversitySydneyAustralia

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