Lewy body pathology

Our knowledge of the underlying pathology in PD began with Frederic H. Lewy’s discovery in 1912 of inclusion bodies in patients with PD [6]. These spherical filamentous inclusions, now known as Lewy bodies (LBs), have been at the centre of discussions about the pathology of this disease for over 100 years. In 1997, Polymeropoulos et al. [7] reported the discovery of a mutation

Histopathological appearance of brain tissue from patients with Parkinson's disease dementia

Fig. 15.1 Histopathological appearance of brain tissue from patients with Parkinson's disease dementia (PD-D). (A) Several cortical neurons at high power containing cortical Lewy bodies. Cortical Lewy bodies typically lack a halo, and they are the strongest pathological feature associated with PD-D. Their density also correlates with specific clinical features in some studies. (B) Nigral Lewy bodies in the cytoplasm of brainstem neurons. These are associated more closely with the motor features of PD. Nigral Lewy bodies usually contain a 'halo' that stains strongly for a-synuclein (images A and B are stained with antibodies directed against a-synuclein). (C) Modified silver stain to demonstrate Alzheimer's neurofibrillary tangles (top) and a senile plaque (bottom) in cortical brain tissue from the medial temporal lobe of a PD patient. Alzheimer's pathological features are not uncommon in PD-D patients, but do not correlate with dementia as closely as synuclein pathology (Lewy bodies and Lewy neurites).

in the gene coding for a pre-synaptic protein called a-synuclein in one Italian kindred and three unrelated Greek families with autosomal dominant PD. Following this finding, Spillantini et al. [8] found that LBs as well as dystrophic processes called Lewy neurites (LNs), with similar immu- nohistochemical properties to LBs, found in patients with idiopathic PD and DLB stained strongly for this protein, yielding clues about the composition of the inclusions. Shortly afterwards, Baba et al. [9] revealed that a-synuclein in LBs was aggregated into fibrils in both sporadic and genetic forms of PD. LBs have since been found to comprise more than 40 proteins, including ubiquitin, tau, heat shock proteins, neurofilaments, aggresomal proteins, and mitochondrial proteins, but a-synuclein is by far the most prominent [10].

Several neurodegenerative diseases have also been found to have inclusions which are immuno- reactive for a-synuclein, including multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type 1. These and others have joined the ranks of PD and DLB to form a new class of disease now referred to as the synucleinopathies [11].

In PD-D, LBs are abundant in cortical structures. Cortical LBs (CLBs) have been described as having a less distinct morphology, particularly when using haematoxylin and eosin staining, and they typically lack the distinctive halo which is classically found in LBs in the substantia nigra (SN) [10]. CLBs are the most specific pathological finding in PD-D and they have consistently been found to correlate with dementia [12-14] (see Fig. 15.1).

 
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