Neurodegenerative diseases
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
- 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
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
Progressive supranuclear palsy
General
Microscopic
- 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).
Binswanger's disease
General
- Multi-infarct dementia affecting subcortical white matter.
- Waste-basket diagnosis; diagnosed if CADASIL and amyloidosis have been excluded.
- Diagnosis has been controversial -- most with this entity (in the past) were diagnosed with Alzheimer's disease.
Microscopic
Features:
- Subcortical lesions that replace the myelin consisting of macrophages.
Prion diseases
Etiology:[10]
- Misfolded cell-surface protein called PrP(C).
Includes:[10]
- Creutzfeldt-Jakob disease (CJD).
- Sporadic fatal insomnia (sFI).
Creutzfeldt-Jakob disease
General
- Commonly abbreviated as CJD.
- Rare.
- Incurable disease.
- Usually diagnosed clinically.
- Characteristic findings:
- Very rapid decline (3-4 months).
- Characteristic (cortex findings on) neuroradiology.
- Characteristic findings:
Variant Creutzfeldt-Jakob disease (vCJD)
- Associated with bovine spongiform encephalopathy.
- Should sample: spleen, lymph nodes, tonsils.[11]
Microscopic
Features:
- Spongy appearance (cytoplasmic vacuolization[12]).
Images:
See also
References
- ↑ 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.
- ↑ 2.0 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/.
- ↑ TN06 PS19
- ↑ 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.
- ↑ Uversky, VN. (Oct 2008). "Alpha-synuclein misfolding and neurodegenerative diseases.". Curr Protein Pept Sci 9 (5): 507-40. PMID 18855701.
- ↑ 6.0 6.1 URL: http://emedicine.medscape.com/article/1151430-overview. Accessed on: 11 November 2010.
- ↑ 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.
- ↑ Kumar P, Kalonia H, Kumar A (2010). "Huntington's disease: pathogenesis to animal models". Pharmacol Rep 62 (1): 1–14. PMID 20360611.
- ↑ URL: http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm. Accessed on: 29 October 2010.
- ↑ 10.0 10.1 Watts JC, Balachandran A, Westaway D (March 2006). "The expanding universe of prion diseases". PLoS Pathog. 2 (3): e26. doi:10.1371/journal.ppat.0020026. PMC 1434791. PMID 16609731. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1434791/.
- ↑ Burton, Julian L.; Rutty, Guy N. (2010). The Hospital Autopsy A Manual of Fundamental Autopsy Practice (3rd ed.). Oxford University Press. pp. 83. ISBN 978-0340965146.
- ↑ URL: http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0I002-PQ01-M.htm. Accessed on: 19 October 2010.