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Dementia with Lewy Body and Parkinson's Disease PatientsPatient, Family, and Clinician Working Together for Better Outcomes$
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J. Eric Ahlskog

Print publication date: 2013

Print ISBN-13: 9780199977567

Published to Oxford Scholarship Online: November 2020

DOI: 10.1093/oso/9780199977567.001.0001

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PRINTED FROM OXFORD SCHOLARSHIP ONLINE (oxford.universitypressscholarship.com). (c) Copyright Oxford University Press, 2021. All Rights Reserved. An individual user may print out a PDF of a single chapter of a monograph in OSO for personal use. date: 24 October 2021

What Is Known about the Cause

What Is Known about the Cause

Chapter:
(p.15) 2 What Is Known about the Cause
Source:
Title Pages
Author(s):

J. Eric Ahlskog

Publisher:
Oxford University Press
DOI:10.1093/oso/9780199977567.003.0006

Most of the research into the cause of Lewy disorders has focused on Parkinson’s disease, since that is the best defined of these conditions and, therefore, the most straightforward to study. Dementia with Lewy bodies (DLB) is more difficult to diagnose with certainty, especially in the early years of the disease. What we collectively learn about Parkinson’s disease will likely be very relevant to our understanding of DLB. Multiple investigations have linked Parkinson’s disease to both environmental exposures and genetic factors. However, these associations have all been modest, and none of them accounts for more than a few percent of the contribution to the cause of sporadic Parkinson’s disease (i.e., the attributable risks are low). These investigations are ongoing and hopefully will soon provide a more complete understanding of the cause(s). Perhaps the most important clue to all Lewy conditions is located in the brain: the Lewy body itself. A recent sophisticated analysis of Lewy bodies revealed approximately 300 different component proteins. However, we already knew that Lewy bodies contain high concentrations of a normal protein called alpha synuclein. In fact, Lewy bodies are conventionally identified under the microscope with antibody stains that specifically bind to alpha synuclein. Could this be the crucial protein among the nearly 300? While the alpha synuclein story is focused on Parkinson’s disease, it may be just as relevant to DLB, as we shall see. The story starts with a large Italian-American family with Parkinson’s disease, studied by Dr. Lawrence Golbe and colleagues at the Robert Wood Johnson Medical Center in New Brunswick, New Jersey. In this rare family, many members of multiple generations had been affected by Parkinson’s disease (with Lewy bodies), consistent with a single gene passed on with dominant inheritance. It took a number of years to identify that abnormal gene, which ultimately was proven to be the gene coding for alpha synuclein. It was quickly discovered that this genetic error is not present in usual cases of Parkinson’s disease.

Keywords:   Braak, Heikko, Farrer, Matthew, Golbe, Lawrence, Lewy neurites, Robert Wood Johnson Medical Center, alpha-synuclein genetic coding

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