Difference between revisions of "Neurodegenerative diseases"

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==Multiple system atrophy==
==Multiple system atrophy==
*Alpha-synuclein-rich glial cytoplasmic inclusions - 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 }}
*Alpha-synuclein-rich glial cytoplasmic inclusions - 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>
</ref>
**Alpha-synuclein is implicated in a number of neurodegenerative diseases.<ref name=pmid18855701>{{Cite journal  | last1 = Uversky | first1 = VN. | title = Alpha-synuclein misfolding and neurodegenerative diseases. | journal = Curr Protein Pept Sci | volume = 9 | issue = 5 | pages = 507-40 | month = Oct | year = 2008 | doi =  | PMID = 18855701 }}</ref>
**Alpha-synuclein is implicated in a number of neurodegenerative diseases.<ref name=pmid18855701>{{Cite journal  | last1 = Uversky | first1 = VN. | title = Alpha-synuclein misfolding and neurodegenerative diseases. | journal = Curr Protein Pept Sci | volume = 9 | issue = 5 | pages = 507-40 | month = Oct | year = 2008 | doi =  | PMID = 18855701 }}</ref>


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===Microscopic===
===Microscopic===
Features:<ref name=pmid1991832/><ref name=psp_emedicine>URL: [http://emedicine.medscape.com/article/1151430-overview http://emedicine.medscape.com/article/1151430-overview]. Accessed on: 11 November 2010.</ref><ref name=pmid19233037>{{cite journal |author=Williams DR, Lees AJ |title=Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges |journal=Lancet Neurol |volume=8 |issue=3 |pages=270–9 |year=2009 |month=March |pmid=19233037 |doi=10.1016/S1474-4422(09)70042-0 |url=}}</ref>
Features:<ref name=pmid19918325>{{cite journal |author=Dickson DW |title=Neuropathology of non-Alzheimer degenerative disorders |journal=Int J Clin Exp Pathol |volume=3 |issue=1 |pages=1–23 |year=2009 |pmid=19918325 |pmc=2776269 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776269/?tool=pubmed}}</ref><ref name=psp_emedicine>URL: [http://emedicine.medscape.com/article/1151430-overview http://emedicine.medscape.com/article/1151430-overview]. Accessed on: 11 November 2010.</ref><ref name=pmid19233037>{{cite journal |author=Williams DR, Lees AJ |title=Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges |journal=Lancet Neurol |volume=8 |issue=3 |pages=270–9 |year=2009 |month=March |pmid=19233037 |doi=10.1016/S1474-4422(09)70042-0 |url=}}</ref>
*Globose neurofibrillary tangles in neurons.
*Globose neurofibrillary tangles in neurons.
*Coiled bodies in oligodendrocytes.
*Coiled bodies in oligodendrocytes.

Revision as of 17:31, 12 November 2010

Neurodegenerative diseases is a big part of neuropathology.

Overview

They are essentially progressive and selective neuron loss. Clinically, they are not unique. They are defined by molecular pathology.[1]

Molecular schema of neurodegenerative disorders:[1]

 
 
 
 
 
 
Neurodegenerative
disorders
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amyloidoses
 
Tauopathies
 
α-synucleinopathies
 
TDP-43
 

Common diseases

Amyloidoses:

  • Alzheimer disease (Abeta).
  • Creutzfeldt-Jakob disease (PrP).

Taupathies:

  • Progressive supranuclear palsy.
  • Pick's disease.

Synucleinopathies:

  • Parkinson disease.
  • Dementia with Lewy bodies.
  • Multiple system atrophy.

TDP-43 proteinopathies:

  • Amyotrophic alteral sclerosis.
  • Frontotemporal lobar degeneration with ubiquitinated inclusions.

Table

Disease/pathology/clinical correlation based on Dickson:[1]

Disease Mutated protein Distribution Clinical Image
Alzheimer disease Abeta (mutated APP) corticolimbic, usu.
spares occipital 		dementia Image?
Creutzfeldt-Jakob disease PrPres (mutated PrP) cortical & basal ganglia dementia (rapid progression),
movement disorder 		Image?
Progressive supranuclear palsy tau 4R basal ganglia, brainstem parkinsonism Image?
Pick disease tau 3R corticolimbic dementia + focal
cortical syndrome 		Image?
Parkinson disease alpha-synuclein brainstem parkinsonism Image?
Dementia with
Lewy bodies 		alpha-synuclein corticolimbic, brainstem dementia + parkinsonism Image?
Multiple system atrophy alpha-synuclein basal ganglia, brainstem, cerebellum parkinsonism, ataxia Image
Amyotrophic lateral
sclerosis (ALS) 		TDP-43 motor neurons spasticity, weakness Image
Frontotemporal lobar
degeneration with
ubiquitinated inclusions 		TDP-43 cortex, basal ganglia dementia, focal cortical syndromes Image?

IHC

  • AT-8 = stains phosphorylated tau.[2]
  • p62; poli-ubiquitin-binding protein p62.[2]
  • TDP-43.

General DDx of dementia

  • Alzheimer's dementia.
  • Vascular.
    • Multi-infarct dementia.
  • Parkinson's associated dementia.
  • Lewy body dementia.
  • Alcohol-related dementia.
  • Fronto-temporal dementia (Pick disease).
  • Multisystem atrophy.

Mnemonic VITAMIN D VEST:[3]

  • Vitamin deficiency (B12, folate, thiamine).
  • Infection (HIV).
  • Trauma.
  • Anoxia.
  • Metabolic (Diabetes).
  • Intracranial tumour.
  • Normal pressure hydrocephalus.
  • Degenerative (Alzheimer's, Huntington's, CJD).
  • Vascular.
  • Endocrine.
  • Space occupying lesion (chronic subdural hematoma).
  • Toxins (alcohol).

Lewy body dementia

  • Parkinsonian features.
  • Hallucinations (visual).
  • Progressive cog. decline with fluctuations.

Multiple system atrophy

  • Alpha-synuclein-rich glial cytoplasmic inclusions - finding at autopsy.[4]
    • Alpha-synuclein is implicated in a number of neurodegenerative diseases.[5]

Progressive supranuclear palsy

General

  • AKA Steele-Richardson-Olszewski syndrome.
  • Diagnosis: clinical.[6]

Microscopic

Features:[1][6][7]

  • Globose neurofibrillary tangles in neurons.
  • Coiled bodies in oligodendrocytes.

Huntington disease

General

  • Autosomal dominant inheritance.
  • Mutation: unstable CAG repeat.[8]

Gross

  • Missing caudate.[9]

Image: Huntington's disease (ouhsc.edu).

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 Dickson DW (2009). "Neuropathology of non-Alzheimer degenerative disorders". Int J Clin Exp Pathol 3 (1): 1–23. PMC 2776269. PMID 19918325. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776269/?tool=pubmed.
  2. ↑ 2.0 2.1 Seelaar H, Klijnsma KY, de Koning I, et al. (May 2010). "Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration". J. Neurol. 257 (5): 747–53. doi:10.1007/s00415-009-5404-z. PMC 2864899. PMID 19946779. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864899/.
  3. ↑ TN06 PS19
  4. ↑ Wenning, GK.; Stefanova, N.; Jellinger, KA.; Poewe, W.; Schlossmacher, MG. (Sep 2008). "Multiple system atrophy: a primary oligodendrogliopathy.". Ann Neurol 64 (3): 239-46. doi:10.1002/ana.21465. PMID 18825660.
  5. ↑ Uversky, VN. (Oct 2008). "Alpha-synuclein misfolding and neurodegenerative diseases.". Curr Protein Pept Sci 9 (5): 507-40. PMID 18855701.
  6. ↑ 6.0 6.1 URL: http://emedicine.medscape.com/article/1151430-overview. Accessed on: 11 November 2010.
  7. ↑ Williams DR, Lees AJ (March 2009). "Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges". Lancet Neurol 8 (3): 270–9. doi:10.1016/S1474-4422(09)70042-0. PMID 19233037.
  8. ↑ Kumar P, Kalonia H, Kumar A (2010). "Huntington's disease: pathogenesis to animal models". Pharmacol Rep 62 (1): 1–14. PMID 20360611.
  9. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm. Accessed on: 29 October 2010.
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