Lewy neurites

Lewy body filaments are made of a-synuclein. Shortly after the identification of the genetic defect responsible for Parkinson s disease in the Contursi kindred, Lewy bodies and Lewy neurites in the substantia nigra from patients with sporadic Parkinson s disease were shown to be strongly immunoreactive for a-synuclein [7] (Fig. 45-3). Subsequently, Lewy body filaments were found to be... 

FIGURE 45-3 Substantia nigra from patients with Parkinson s disease immunostained for a-synuclein. (A) Two pigmented nerve cells, each containing an a-synuclein-positive Lewy body. Lewy neurites (small arrows) are also immunopositive. Scale bar 20 pm. (B) Pigmented nerve cell with two a-synuclein-positive Lewy bodies. Scale bar 8 pm. (C) a-Synuclein-positive extracellular Lewy body. Scale bar 4pm. 

PD a-Synuclein Substantia nigra, cortex Lewy bodies and Lewy neurites... 

The degenerative process of idiopathic PD (iPD) is associated with the anatomical progression of CEBl-synuclein into select neurons. It is an aggregate of the mis-folded protein and appears in dendrites and axons, Lewy neurites (LNs), as well as punctuate structures and/or Lewy bodies (LBs) in the somata of involved nerve cells. It is thought that only projection neurons with a long axon become involved, whereas short-axoned cells resist the pathology. It has been proposed that vulnerable brain regions in PD are anatomically interconnected. 

PD pathology is characterized by threadlike proteinaceous neurite inclusions and intracellular Lewy bodies (Fig. 14.1) occurring exclusively in unmyelinated fibers. In pathological stage I and II of the disease, first Lewy neurites, then Lewy bodies appear almost simultaneously in the olfactory bulb and the dorsal visceromotor nucleus of the vagal nerve. Degeneration in the olfactory bulb seems to be very slow. 

Early signs of Lewy neurites and Lewy bodies can also be found in Auerbach s... 

Interestingly, in patients with autosomal recessive juvenile parkinsonism, no Lewy bodies or Lewy neurites are found at autopsy [23]. 

In PD, there is a loss of neurons in the substantia nigra and elsewhere in the brain in association with the presence of protein deposits in the cytoplasm of neurons (Lewy bodies) and thread-like proteinaceous inclusions within Lewy neurites. 

Parkinson s disease is a common neurodegenerative syndrome characterized by loss of dopaminergic neurons in the substantia nigra, formation of filamentous intraneuronal inclusions (Lewy bodies) and an extrapyramidal movement disorder. Mutations in the a-synuclein gene are linked to familial Parkinson s disease, and a-synuclein accumulates in Lewy bodies and Lewy neurites. Normal and mutant forms of a-synuclein were expressed in Drosophila and produced adult-onset loss of dopaminergic neurons, filamentous intraneuronal inclusions containing a-synuclein and locomotor dysfunction. The Drosophila model thus recapitulates the essential features of the human disorder and makes possible a powerful genetic approach to Parkinson s disease. 

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