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Prionopathies: | Prionopathies: | ||
*Creutzfeldt-Jakob disease (PrP). | *Creutzfeldt-Jakob disease (PrP). | ||
'''Note:''' Some people consider α-synuclein as a prion-like protein.<ref>{{Cite journal | last1 = Watts | first1 = JC. | title = Calling α-synuclein a prion is scientifically justifiable. | journal = Acta Neuropathol | volume = 138 | issue = 4 | pages = 505-508 | month = Oct | year = 2019 | doi = 10.1007/s00401-019-02058-0 | PMID = 31407029 }}</ref> | |||
====Table==== | ====Table==== | ||
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===Ubiquitin=== | ===Ubiquitin=== | ||
*Marks proteins for recycling. | *Marks proteins for recycling. | ||
*Stains Barr bodies in hippocampal granule cells<ref> {{Cite journal | last1 = Gelpi | first1 = E. | title = Clinical Neuropathology teaching case 3-2015: female or male brain? Anti-ubiquitin visualizes Barr bodies in hippocampal granule cells which allows the determination of gender in human brains. | journal = Clin Neuropathol | volume = 34 | issue = 3 | pages = 115-6 | month = | year = | doi = | PMID = 25909954 }}</ref> | |||
===p62=== | |||
*p62; poli-ubiquitin-binding protein p62.<ref name=pmid19946779/> | *p62; poli-ubiquitin-binding protein p62.<ref name=pmid19946779/> | ||
===Microscopic=== | ===Microscopic=== | ||
Look for: | Look for: | ||
*Lewy bodies. | * Lewy bodies and extracellular pigment in neuromelanin-containing nuclei (SN, LC, DVN) -> PD. | ||
* Spongiform vacuolation in the neuropil (seen in Prion disease and FTLD-TDP). | |||
* Neurofibrillar tangles (pyramidal layer of dentate gyrus). | |||
* Granulovacuolar degeneration (granules within cytoplasmic vacuoles, mainly in the hippocampal pyramidal neurons, seen in AD). | |||
* Cores of amyloid plaqyes. | |||
* Cotton wool plaques (seen in familiar AD). | |||
* Pick cells (balloned neurons in frontal cortex). | |||
* Pick bodies (granular layer of dentate gyrus). | |||
* Extensive astrogliosis (striatonigral degeneration, hepatic encephalopathy). | |||
* Corpora amylacea in the cornu ammonis may be increased in neurodegenerative diseases. <ref>{{Cite journal | last1 = Kovacs | first1 = GG. | last2 = Risser | first2 = D. | title = Clinical Neuropathology image 6-2014: Corpora amylacea replacing cornu ammonis (CACA). | journal = Clin Neuropathol | volume = 33 | issue = 6 | pages = 378-9 | month = | year = | doi = | PMID = 25343241 }}</ref> | * Corpora amylacea in the cornu ammonis may be increased in neurodegenerative diseases. <ref>{{Cite journal | last1 = Kovacs | first1 = GG. | last2 = Risser | first2 = D. | title = Clinical Neuropathology image 6-2014: Corpora amylacea replacing cornu ammonis (CACA). | journal = Clin Neuropathol | volume = 33 | issue = 6 | pages = 378-9 | month = | year = | doi = | PMID = 25343241 }}</ref> | ||
<gallery> | |||
File:213-09-11-Congo Red Lewy body.tif|Lewy body | |||
File:Amyloid plaques alzheimer disease HE stain.jpg|Cotton wool plaques | |||
File:Neurofibrillary tangles in the Hippocampus of an old person with Alzheimer-related pathology, HE 3.JPG|Neurofibrillary tangles | |||
File:SpongiformChangeCJD.jpg | Spongiform vacuolation | |||
</gallery> | |||
=Clinical perspective= | =Clinical perspective= | ||
*Correlations between clinical signs and molecular can be poor. | |||
**Example: The MAPT A152T gene mutation may cause clinical symptoms matching AD, [[Neurodegenerative diseases#Corticobasal degeneration|CBD]], [[Neurodegenerative diseases#Progressive supranuclear palys|PSP]] and [[Neurodegenerative diseases#Lewy body disease|LBD]].<ref>{{Cite journal | last1 = Coppola | first1 = G. | last2 = Chinnathambi | first2 = S. | last3 = Lee | first3 = JJ. | last4 = Dombroski | first4 = BA. | last5 = Baker | first5 = MC. | last6 = Soto-Ortolaza | first6 = AI. | last7 = Lee | first7 = SE. | last8 = Klein | first8 = E. | last9 = Huang | first9 = AY. | title = Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases. | journal = Hum Mol Genet | volume = 21 | issue = 15 | pages = 3500-12 | month = Aug | year = 2012 | doi = 10.1093/hmg/dds161 | PMID = 22556362 }}</ref> | |||
===Dementia general (mostly useless) DDx=== | ===Dementia general (mostly useless) DDx=== | ||
*[[Alzheimer's disease|Alzheimer's]] dementia - most common. | *[[Alzheimer's disease|Alzheimer's]] dementia - most common. | ||
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*Misfolded cell-surface protein called PrP<sup>SC</sup>. | *Misfolded cell-surface protein called PrP<sup>SC</sup>. | ||
**This is derived from the protein ''PrP<sup>C</sup>'' encoded by the ''PRNP'' gene. | **This is derived from the protein ''PrP<sup>C</sup>'' encoded by the ''PRNP'' gene. | ||
*Different genetics strains are associated with varying clinical phenotype.<ref>{{Cite journal | last1 = Monari | first1 = L. | last2 = Chen | first2 = SG. | last3 = Brown | first3 = P. | last4 = Parchi | first4 = P. | last5 = Petersen | first5 = RB. | last6 = Mikol | first6 = J. | last7 = Gray | first7 = F. | last8 = Cortelli | first8 = P. | last9 = Montagna | first9 = P. | title = Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. | journal = Proc Natl Acad Sci U S A | volume = 91 | issue = 7 | pages = 2839-42 | month = Mar | year = 1994 | doi = 10.1073/pnas.91.7.2839 | PMID = 7908444 }}</ref> | |||
Includes: | Includes: | ||
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Note: | Note: | ||
*Spongiform changes may be seen in [[ALS]], [[Alzheimer's disease]] and Lewy body disease (e.g. [[Parkinson disease]]); however, the changes are only in the upper cortex and not diffuse.<ref>{{Ref APBR|419 Q4}}</ref> | *Spongiform changes may be seen in [[ALS]], [[Alzheimer's disease]] and Lewy body disease (e.g. [[Parkinson disease]]); however, the changes are only in the upper cortex and not diffuse.<ref>{{Ref APBR|419 Q4}}</ref> | ||
===Molecular=== | |||
*The CJD phenotype is associated with a PRNP D178N mutation and valine polymorphism at codon 129 (D178N-129V). | |||
** Note: A Met129 polymorphism will cause Fatal familiar insomnia in the setting of the same PRNP D178N mutation. <ref>{{Cite journal | last1 = Goldfarb | first1 = LG. | last2 = Petersen | first2 = RB. | last3 = Tabaton | first3 = M. | last4 = Brown | first4 = P. | last5 = LeBlanc | first5 = AC. | last6 = Montagna | first6 = P. | last7 = Cortelli | first7 = P. | last8 = Julien | first8 = J. | last9 = Vital | first9 = C. | title = Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. | journal = Science | volume = 258 | issue = 5083 | pages = 806-8 | month = Oct | year = 1992 | doi = 10.1126/science.1439789 | PMID = 1439789 }}</ref> | |||
<gallery> | <gallery> | ||
| Line 505: | Line 534: | ||
*Neuronal loss and gliosis (absent in minimal-change MSA). | *Neuronal loss and gliosis (absent in minimal-change MSA). | ||
*Alpha-synuclein-rich glial and neuronal cytoplasmic inclusions in white matter (finding at autopsy).<ref name=pmid18825660>{{Cite journal | last1 = Wenning | first1 = GK. | last2 = Stefanova | first2 = N. | last3 = Jellinger | first3 = KA. | last4 = Poewe | first4 = W. | last5 = Schlossmacher | first5 = MG. | title = Multiple system atrophy: a primary oligodendrogliopathy. | journal = Ann Neurol | volume = 64 | issue = 3 | pages = 239-46 | month = Sep | year = 2008 | doi = 10.1002/ana.21465 | PMID = 18825660 }}</ref> | *Alpha-synuclein-rich glial and neuronal cytoplasmic inclusions in white matter (finding at autopsy).<ref name=pmid18825660>{{Cite journal | last1 = Wenning | first1 = GK. | last2 = Stefanova | first2 = N. | last3 = Jellinger | first3 = KA. | last4 = Poewe | first4 = W. | last5 = Schlossmacher | first5 = MG. | title = Multiple system atrophy: a primary oligodendrogliopathy. | journal = Ann Neurol | volume = 64 | issue = 3 | pages = 239-46 | month = Sep | year = 2008 | doi = 10.1002/ana.21465 | PMID = 18825660 }}</ref> | ||
**Inclusions in oligodendrocytes (triangular, flame-like or sickle-shaped) are definitive diagnostic for MSA.<ref>MUN. 16 November 2010.</ref><ref>{{cite journal | | **Inclusions in oligodendrocytes (triangular, flame-like or sickle-shaped) are definitive diagnostic for MSA.<ref>MUN. 16 November 2010.</ref><ref>{{cite journal |authors=Trojanowski JQ, Revesz T |title=Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy |journal=Neuropathol. Appl. Neurobiol. |volume=33 |issue=6 |pages=615–20 |year=2007 |pmid=17990994 |doi=10.1111/j.1365-2990.2007.00907.x |url=}}</ref> | ||
**Inclusions usu. abundant in basal ganglia, substantia nigra, pontine nuclei, medulla and cerebellum. | **Inclusions usu. abundant in basal ganglia, substantia nigra, pontine nuclei, medulla and cerebellum. | ||
*Pons and Putamen: | *Pons and Putamen: | ||