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Amyloid and Neurodegeneration: Alzheimer's Disease and Retinal Degeneration

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Book cover Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Deposits of specific proteins are believed to cause a large group of degenerative diseases. Given that the neurodegenerative disease, prion, is an infectious protein deposit disorder, a common theme of degeneration mediated by toxic aggregates has been developed. However, the mechanisms of cellular toxicity induced by protein deposits remain a mystery and although new diseases are being added to the list and treatments for these diseases remain elusive. Alzheimer's disease (AD) and age-related macular degeneration (AMD) are two prototypic neurodegenerative diseases that are characterized by extracellular protein deposits in the brain and the eye, respectively. Indeed, the amyloid β peptide (Aβ) deposited in the core of senile plaques and cerebrovascular amyloid of AD are also found in drusen—extracellular deposits found between the retinal pigmented epithelium (RPE) and Bruch's membrane—of patients suffering from AMD. Since amyloid deposits in the brain are fostered by multiple genetic and environmental factors that cause AD, and certain forms of Aβ are neurotoxic, it has been attributed a central place in the pathogenesis of AD. Finding Aβ in the drusen suggests that the two diseases may share common pathogenic mechanisms and that lessons learnt from one disease can be applied to the other even though clinically AD does not appear to increase the risk of AMD and vice versa. However, AD patients suffer an increase in the risk of glaucoma, a retinal disease affecting the ganglion cells that collect the integrated information from the eye and communicate with the brain via the optic nerve. Since the cause and mechanisms of neurodegeneration are poorly understood in both diseases, this is a very important fundamental and unanswered question. In this chapter, we discuss the salient features of AD and retinal degeneration (including AMD and glaucoma) and attempt to integrate the major features to identify common pathogenic pathways that cause both diseases.

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Abbreviations

(Aβ40):

40-residue species

(Aβ):

amyloid β peptide

(ABCR):

ATP-binding cassette transporter

(ACAT):

acyltransferase

(AD):

Alzheimer's disease

(AMD):

age-related macular degeneration

(APP):

Aβ precursor

(ApoE):

apolipoprotein E

(BBS):

Bardet-Biedl syndrome

(CFB):

complement factor B

(CFB):

complement factor B

(CFH):

complement factor H

(CFH) :

complement factor H

(CHM):

choroideremia gene

(CNS):

central nervous system

(CRD):

Cone-Rod Dystrophy

(CRP):

C-reactive protein

(CRP):

C-reactive protein

(cygb):

cytoglobin

(DHRD):

Doyne honeycomb retinal dystrophy

(ML):

Malattia Leventinese

(FAD):

familial AD

(GA):

Geographic Atrophy

(HDL):

high-density lipoprotein

(JMD):

juvenile forms of macular degeneration

(MAC):

membrane attack complex

(MAPT):

microtubule-associated protein tau

(MCI):

mild cognitive impairment

(NFTs):

neurofibrillary tangles

(Ngb):

neuroglobin

(NSAIDs):

nonsteroidal anti-inflammatory drugs

(OCA):

oculocutaneous albinism

(PUFA):

polyunsaturated fatty acid-rich

(ROS):

reactive oxygen species

(ROS):

rod outer segment

(RP):

retinitis pigmentosa

(RPE):

retinal-pigmented epithelium

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Acknowledgments

We thank the American Health Assistance Foundation for providing grants to KS and BR and the NIH (NIA) for support to KS. We also thank Ms Meera Parasuraman and Ms Christina Demos for reading the manuscript and providing useful criticism.

Authors
  1. A. Prakasam
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  2. C. Venugopal
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  3. A. Suram
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  4. J. Pacheco-Quinto
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  5. Y. Zhou
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  6. M. A. Pappolla
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  7. K. A. Sharpe
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  8. D. K. Lahiri
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  9. N. H. Greig
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  10. B. Rohrer
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  11. K. Sambamurti
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 29425, 96 Jonathan Lucas Street, Suite 309, Charleston, SC, USA

    Naren Banik

  3. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 29209, 6439 Garners Ferry Road Building 2, Room C11, Columbia, SC, USA

    Swapan K. Ray

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Prakasam, A. et al. (2009). Amyloid and Neurodegeneration: Alzheimer's Disease and Retinal Degeneration. In: Lajtha, A., Banik, N., Ray, S.K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30375-8_7

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