IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 1(3):217-231;2008

Review Article
Genetic Neuropathology of Parkinson’s disease

Mark R Cookson, John Hardy and Patrick A Lewis

Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda MD 20892-3707, USA; Reta Lilla Weston Laboratories
and Dept of Molecular Neuroscience, Institute of Neurology UCL, Queen Square, London WC1N 3BG, UK

Received 31 Aug 2007; accepted and available online 1 January 2008

Abstract: Parkinson’s disease (PD) has long been thought of as a sporadic entity, perhaps with an environmental etiology.  However, recent
genetic discoveries have challenged this view, as there are many families with Mendelian inheritance of diseases that clinically resemble PD.  
Here, we will review in detail the neuropathological data relating to familial cases of PD.  We will discuss the complicated relationships
between the genetically defined cases and the two key pathological events seen in PD, namely loss of dopaminergic neurons in the substantia
nigra pars compacts and the formation of protein inclusions, Lewy bodies, in the neurons that survive to the end stage of the disease course.  
These observations will be synthesized into an overall scheme that emphasizes the two key aspects of the neuropathology as distinct events
and suggest that each gene tells us something a little different about the neuropathology of PD. (IJCEP708017).

Key Words: Parkinson’s disease; parkinsonism; alpha-synuclein; LRRK2; parkin; tau; neuropathology

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Address all correspondence to: Mark R. Cookson, PhD, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda,
MD 20892-3707, USA. Tel: 301-451-3870; Fax: 301-480-0335; Email: