granulovacuolar change
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Introduction
First applied by Simchowicz in 1911 to a neuronal appearance in senile dementia.
Etiology
- one theory suggests that GV-change represents autophagy of cytoskeletal proteins.
Histology
- GV-change is largely confined to the pyramidal cells of the hippocampus, but may extend into the adjacent subiculum
- one or more vacuoles 3-5 um in diameter, each containing a central dot or granule, 1-2 um across characterize GV change.
- several vacuoles are common in an affected cell, & when they are numerous, the cell may bulge & the nucleus may be displaced to one side.
- GV-change is easily seen with hematoxylin-eosin (H&E) staining & with many silver stains
- electron microscopy shows cytoplasmic inclusions with a translucent matrix & an electron-dense granular core.
Pathology
- GV-change is rarely seen before age 65, but become increasingly common with age.
- at age 90, 3/4 autopsies show evidence of GV-change, with < 9% of pyramidal cells of the hippocampus affected in non-demented patients
- in contrast, demented patients mayas much as 20-50% of pyramidal neurons with GV-change.
Components of granules: (immunocytochemistry)
- neurofilaments[1]
- tubulin[1]
- heme oxygenase-1[2]
- phosphorylated tau of neurofibrillary tangles[1]
- casein kinase 1[3]
- caspase 3[4]
- ubiquitin
- advanced glycation end products (AGE)[5]
Disorders showing GV change:
- normal aging
- Alzheimer's disease
- supranuclear palsy*
- amyotrophic lateral sclerosis
- parkinson-dementia of Guam
- tuberous sclerosis#
* GV-change also seen in red nucleus & other brainstem nuclei
# case report of parietal GV-change
More general terms
References
- ↑ 1.0 1.1 1.2 1.3 Greenfield's Neuropathology, 5th edition, Adams JH & Duchen LW, (eds), Oxfird University Press, NY, 1992, pg 1313
- ↑ 2.0 2.1 Smith MA et al Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. Am J Pathol. 1994 Jul;145(1):42-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8030754 [Heme Oxygenase-1]
- ↑ 3.0 3.1 Ghoshal N et al A new molecular link between the fibrillar and granulovacuolar lesions of Alzheimer's disease. Am J Pathol. 1999 Oct;155(4):1163-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10514399
- ↑ 4.0 4.1 Stadelmann C et al Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death. Am J Pathol. 1999 Nov;155(5):1459-66. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10550301
- ↑ 5.0 5.1 Sasaki N et al Advanced glycation end products in Alzheimer's disease and other neurodegenerative diseases. Am J Pathol. 1998 Oct;153(4):1149-55. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9777946