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Table of Contents
Definition / general | Uses by pathologists | Clinical features | Microscopic (histologic) images | Positive stains | Additional referencesCite this page: Alpha-synuclein. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsalphasynuclein.html. Accessed July 12th, 2017.
Definition / general
- Member of the synuclein family of soluble proteins (alpha-synuclein, beta-synuclein and gamma-synuclein) that are commonly present in CNS of vertebrates
- Expressed in the neocortex, hippocampus, substantia niagra, thalamus and cerebellum
- Main location is within the presynaptic terminals of neurons in both membrane-bound and cytosolic free forms
- Can be seen in neuroglial cells and melanocytic cells; highly expressed in the neuronal mitochondria of the olfactory bulb, hippocampus, striatum and thalamus
- Three isoforms have been isolated by alternative splicing
- Most research is the full length isoform with 140 amino acids
- Others are alpha-synuclein-112 and alpha-synuclein-126 (Wikipedia)
Uses by pathologists
- Diagnosis of (a) Parkinson disease (PD) / brainstem predominant type of Lewy body disease, and (b) dementia with Lewy bodies (DLB), the two most frequent synucleinopathies.
- These neurodegenerative multisystem disorders have widespread occurrence of α-synuclein containing deposits in the central, peripheral, and autonomic systems. For both, staging/classification systems are based on semiquantitative assessment of the distribution and progression pattern of α-synuclein pathology, which are considered to be linked to clinical dysfunction (Biochimica et Biophysica Acta;2009:1792;730, Int J Clin Exp Pathol 2014;7:1714, Mov Disord 2016;31:193
Clinical features
- Forms insoluble aggregates in the group of pathological disorders known as synucleopathies, characterized by:
- Formation of neuronal Lewy bodies and Lewy neurites in idiopathic Parkinson disease and dementia with Lewy bodies
- Oligodendroglial cytoplasmic inclusions in multiple system atrophy
- Large axonal spheroids in several rarer neuroaxonal dystrophies
- Both the sporadic and the familial form of Alzheimer disease also demonstrate alpha-synuclein protein
- In recent years, several studies have shown that alpha-synuclein aggregation can also be detected outside the central nervous system, particularly in the enteric nervous system of the gastrointestinal tract of PD patients using immunohistochemistry
- This has the potential to enable an early diagnosis of the disease as well as enhance the neuroprotective effects of the available therapeutic modalities
Microscopic (histologic) images
Images hosted on PathOut servers:
Lewy body in Parkinson disease
Cellular inclusions and
neuritis plaques
In cortex: (A) no staining and (B) synaptic staining; In substantia nigra: neurons with (C) > S-immunoreactive (IR) aggregates (arrows), (D) >S-IR neurites / neuropil threads (arrowheads), and (E) > S-IR macrophages (open arrow); (F) punctate cytoplasmic labeling; (G) punctate cytoplasmic labeling with ovoid inclusions; (H) multiple rounded inclusions; and (I) extracellular Lewy bodyYlike inclusion.
Positive stains
- Brain tissue: neocortex, hippocampus, substantia niagra, thalamus and cerebellum (within the presynaptic terminals of neurons in both membrane bound and cytosolic free forms)
- Olfactory bulb, hippocampus, striatum and thalamus (highly expressed in mitochondria)
- Also neuroglial cells, melanocytic cells
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