Revision as of 08:34, 7 May 2015

Neurodegenerative diseases is a big part of neuropathology. It includes some discussion of dementia.

Overview

Neurodegenerative disease = essentially progressive and selective neuron loss.
Clinically, they are not unique, e.g. dementia can be caused by several diseases (with different molecular etiologies).
- Each syndrome (e.g. dementia, parkinsonism, ataxia) has a most common etiology and a DDx.
They are defined by molecular pathology.^[1]
- The diseases are due to the accumulation of abnormal protein.
  - The amino acid sequence of the protein may be completely normal. The problem may just be folding/protein conformation.

Molecular schema of neurodegenerative disorders:^[1]

Neurodegenerative
disorders

Amyloidoses

Tauopathies

α-synucleinopathies

TDP-43

Common diseases

Amyloidoses:

Alzheimer disease (Abeta).

'Pure' tauopathies:

Progressive supranuclear palsy.
Pick's disease.
Corticobasal degeneration.
FTDP-17.
Dementia pugilistica.

Synucleinopathies:^[2]

TDP-43 proteinopathies:

Amyotrophic lateral sclerosis.
Frontotemporal lobar degeneration.

FUS proteinopathies:

Amyotrophic lateral sclerosis.
Frontotemporal lobar degeneration.

Prionopathies:

Creutzfeldt-Jakob disease (PrP).

Table

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

Disease	Mutated protein	Distribution	Clinical	Histology	Image
Alzheimer disease	Abeta (mutated APP)	corticolimbic, usu. spares occipital	dementia	plaques, neurofibrillary tangles	[1]
Creutzfeldt-Jakob disease	PrP^res (mutated PrP)	cortical & basal ganglia	dementia (rapid progression), movement disorder	cytoplasmic vacuolization, PrP+ve plaques, Kuru plaques (MV2 variant)	[2]
Parkinson disease	alpha-synuclein	brainstem	parkinsonism	Lewy bodies in substantia nigra and locus coeruleus	[3] [4]
Dementia with Lewy bodies	alpha-synuclein	corticolimbic, brainstem	dementia + parkinsonism	Lewy bodies brainstem and cortical, tangles	[5] [6]
Multiple system atrophy	alpha-synuclein	basal ganglia, brainstem, cerebellum	parkinsonism, ataxia	Papp-Lantos inclusions (cytoplasmic deposits in oligodendrocytes)^[3]	[7]
Amyotrophic lateral sclerosis (ALS)	TDP-43	motor neurons	spasticity, weakness	motor neuron loss, TDP-43+ve, TAF15-ve, EWS-ve inclusions in motor neurons	[8]
Frontotemporal lobar degeneration with TDP-43 (FTLD-TDP)	TDP-43	cortex, basal ganglia	dementia, focal cortical syndromes	histology depends on (type 1-4), ubiquitin and TDP-43+ve, tau and FUS-ve	[9]
Frontotemporal lobar degeneration with FUS (FTLD-FUS)	FUS	cortex, medulla, hippocampus, and motor cells of the spinal cord	dementia, cases classified as FTLD-U, NIFID and BIBD	FUS+ve, TAF15+ve, EWS+ve cytoplasmic & intranuclear inclusions, neuritic threads	[10]
Progressive supranuclear palsy (FTLD-tau)	tau 4R	basal ganglia, brainstem	atypical parkinsonism with early gait instability, falls, and supranuclear gaze palsy	tau-positive globose neurofibrillary tangles in neurons, tufted astrocytes, coiled bodies in oligodendrocytes	[11]
Pick disease (FTLD-tau)	tau 3R	corticolimbic	dementia + focal cortical syndrome	Intraneuronal argyrophilic inclusions (Pick body)	[12]
Corticobasal degeneration (CBD) (FTLD-tau)	tau 4R	cortical, basal ganglia	dementia + movement disorder (Parkinson-plus syndrome)	ballooned neurons, astrocytic plaques, pretangles in basal nucleus	[13]
Argryophilic grain disease (AGD) (FTLD-tau)	tau 4R	medial temporal lobe, limbic structures	late-onset amnestic syndrome	Argyrophilic grains (also found unspecific in elederly)	[14]

Immunohistochemistry

Alpha-synuclein

Look for:

Lewy bodies (seen in Parkinson's d., Dementia with Lewy bodies) = round cytoplasmic eosinophilic body +/- pale halo.

Tau

AT8 = stains phosphorylated tau.^[4]
- AT = anti-tau.
- Stains tau 4R and tau 3R.^[5]

TDP-43

May accumulate due to a progranulin mutation.

Microscopic

TDP-43 - normally in the nucleus.
- Pathologic: Micrograph (label B) - neurites, skein-like formations (ama-assn.org)^[6]
  - Fibrillar or skein-like formations = cytoplasmic staining.
    - "Skein" = yarn or thread wound on a reel or flock of birds in flight.^[7]
  - Neurites = "squiggly appearance"; "worm-like appearance".

Ubiquitin

Marks proteins for recycling.

Microscopic

p62; poli-ubiquitin-binding protein p62.^[4]

Look for:

Lewy bodies. (???)

Clinical perspective

Dementia general (mostly useless) DDx

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

Mnemonic

Dementia mnemonic VITAMIN D VEST:^[8]

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).

Functional anatomy of dementia

Hippocampus (essential for forming new memories).
Frontal lobe (essential for retrieval of memories).

Parkinsonism causes

Parkinson's disease ^[9]
Dementia with Lewy bodies.
Multiple system atrophy (MSA).^[10]
Progressive supranuclear palsy (PSP).^[11]
Drug induced (valproic acid, MPTP).^[12]^[13]
Vascular. ^[14]
Postencephalitic. ^[15]
Tramuatic (Dementia pugilistica).^[16]

Amyloidoses

Alzheimer disease

General

Onset: episodic memory loss.
Diagnosis is clinical & pathologic.
- Pathologic finding alone are not diagnostic.
Seen in conjunction with vascular amyloid deposition; see cerebral amyloid angiopathy.

Genetics

Genes associated with Alzheimer disease:^[17]

Amyloid precursor protein (APP).
- On chromosome 21 - may explain why Trisomy 21 (Down syndrome) increases the risk of Alzheimer disease.^[18]
Presenilin 1 (PSEN1).^[19]
Presenilin 2 (PSEN2).^[20]
Apolipoprotein E (APOE)^[21] - specifically the epsilon-4 allele.

Gross

Features:

Temporal atrophy, esp. hippocampus.
Dilation of:
- Lateral ventricles.
- Third ventricle.

Gross/microscopic - disease spread by NF tangles (staging):^[22]

Alzheimer "spreads" in a reproducible pattern:
- Stage I-II: entorhinal cortex.
- Stage III-IV: inferior aspect of brain.
- Stage V-VI: limbic system.

Minimal sampling:

Frontal, parietal & temporal lobe
Hippocampus and entorhinal cortex

Additional sampling:

Basal ganglia
Cerebellum
Midbrain (including substantia nigra)
Occipital cortex

Images

Alzheimer's brain. (WC/NIH)
Alzheimer's brain macroscopy (top) vs control (bottom). (WC/Hersenbank)
Alois Alzheimer provided a first description of the pathology. (NLM)

Microscopic

Features:

Neurofibrillary tangles.
- Consists of tau.
- Location: hippocampus, cerebral cortex, hypothalamus.
- Dementia severity correlates better with NF tangles number than senile plaque number.^[23]
- Six-tiered scoring method to assess tangle load ^[24]
- Images: tangles - schematic (pakmed.net)^[25], tangle (washington.edu).^[26]
Senile plaques (AKA neuritic plaques).
- Consists of two components:
  1. Centre - radiates.
    - Consists of Abeta amyloid
  2. Neurites - swollen axons.
- Considered to be more specific for Alzheimer's than NF tangles.
  - How to remember: senile plaques = specific.
- There is a CERAD staging system for senile plaque load: 0 (none), I (mild), II (moderate), III (severe).^[27]
- Images: senile plaques (utah.edu)^[28] senile plaques - beta-APP - high mag. (WC).
Neuron loss.
+/-Cerebral amyloid angiopathy.

Images

Neuritic plaques with amyloid core in HE. (WC/jensflorian)
Neuritic plaques in Gallays silver impregnation. (WC/jensflorian)
Neuritic plaques with amyloid core in Bodian stain. (WC/KGH)
Plaques with Abeta IHC. (WC/Nephron)
Neurofibrillary tangles in HE. (WC/Patho)
Tau IHC highlighting tangles. (WC/Patho)
Tangles in Gallays silver impregnation.(WC/Patho)
HE stain with ghost tangles and Hirano bodies in AD. (WC/Patho)
HE stain with granulovaculolar degeneration in AD. (WC/Patho)

Classification

NIA/AA Guidelines: "ABC" scoring method ^[29]

(A) assessment of amyloid b deposits
(B) staging of neurofibrillary tangles
(C) scoring of neuritic plaques

(A) abeta plaques (Thal phase)^[30]	(B) Neurofibrillary tangles (Braak stage) ^[31]	(C) neuritic plaques (CERAD) ^[32]
(A0) 0	(B0) 0	(C0) none
(A1) 1 (temporal),2 (+frontal, +CA1)	(B1) I,II (transentorhinal)	(C1) sparse (1–5 neuritic plaques/1 mm2)
(A2) 3 (+diencephalon, +striatum)	(B2) III,IV (limbic)	(C2) moderate(6–19 neuritic plaques/1 mm2)
(A3) 4 (+brainstem),5 (+cerebellum, +pons)	(B3) V,VI (neocortical)	(C3) frequent(>20 neuritic plaques/1 mm2)

The ABC score is a good indicator for the likelihood of dementia.

Example: Cerebellar abeta deposits (A3) + tangles in entorhinal cortex and few temporal (B2), + 15 neuritic plaques per 1 mm2 (C2) -> (A3, B3, C2): intermediate AD level change.

Notes:

Abeta amyloid:
- Derived from amyloid precursor protein (APP).
  - APP:
    - Rapid axonal transport - useful as a marker of axonal injury.
    - Function currently not known.
Tau:
- Important in microtubule assembly.

Prion diseases

General

Etiology:^[33]

Misfolded cell-surface protein called PrP^SC.
- This is derived from the protein PrP^C encoded by the PRNP gene.

Includes:

Creutzfeldt-Jakob disease (CJD).
Sporadic fatal insomnia (sFI).^[33]
Fatal familial insomnia (FFI).^[34]^[35]
Gestmann-Straussler-Scheinker syndrome (GSS) - due to PRNP gene mutations.^[36]

IHC

PrP^C:^[34]

Congo red +ve.
PAS +ve.

Creutzfeldt-Jakob disease

Commonly abbreviated as CJD.

General

Rare.
Incurable disease.

Usually diagnosed clinically:

Characteristic findings:
- Very rapid decline (3-4 months).
- Characteristic (cortex findings on) neuroradiology.

Variant Creutzfeldt-Jakob disease

Abbreviated vCJD.

General

Associated with bovine spongiform encephalopathy (AKA mad cow disease).
Should sample: spleen, lymph nodes, tonsils.^[37]

Microscopic

Features:

Spongy appearance (cytoplasmic vacuolization^[38]).

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.^[39]

Images

CJD. (WC/DRdoubleB)
vCJD - prion protein immunostain. (WC/Sbrandner)

CJD - several cases (upmc.edu).

Alpha-synucleinopathies

Without clincial information Parkinson's disease and Dementia with Lewy bodies cannot separated in histology.

Dementia with Lewy bodies

General

Clinical features:

Parkinsonian features.
Hallucinations (visual).
Progressive cognitive decline with fluctuations.

Microscopic

Features:

Lewy bodies.
Lewy neurites.

Note: Cortical Lewy bodies are easily missed in HE.

IHC

Alpha-synuclein +ve.

Images

Lewy bodies in frontal cortex of DLB. (WC/jensflorian)
Alpha-synculein IHC showing cortical Lewy bodies. (WC/jensflorian)
Alpha-synculein IHC showing Lewy Neurites in DLB. (WC/jensflorian)

Parkinson disease

General

Common - often sporadic.
May be genetic.

Clinical TRAP:^[40]

Tremor.
Rigidity.
Akinesia.
Postural instability.

Genetics:^[41]

LRRK2 gene^[42] - autosomal dominant.
PARK2 gene (parkin)^[43] - autosomal recessive.

Gross

Features:^[44]

Abnormally pale substantia nigra.
- Pigmentation increases with age.
Pale locus ceruleus.

Notes:

Substantia nigra is a midbrain structure.
- Image: Midbrain - schematic (WC).

Microscopic

Features:^[44]

Loss of pigmented (catecholaminergic) neurons in the substantia nigra and locus ceruleus.
Gliosis - due to neuron loss.
Lewy bodies (in remaining neurons) - key feature.
- Eosinophilic cytoplasmic inclusion with "dense" (darker) core and pale (surrounding) halo.
  - Consist of filaments composed of alpha-synuclein.
Lewy neurites - alpha-synuclein positive processes.

IHC

Alpha-synuclein +ve.

Images

Schematic progression of PD (PLOSone/Jubault et al.).
Lewy body (HE, left) and Lewy neurite (aSyn IHC, right).
Alpha-synculein positive Lewy body (WC/Marvin101).
Lewy body and Lewy neurites (WC/Suraj Rajan).

Molecular

Hereditary forms in less than 10% of the cases
- Involved genes are consecutively labeled PARK1, PARK2....

Multiple system atrophy

Multiple system atrophy is a neurodegenerative disease of the parkinsonism-plus disorder group.

General

Clinical findings variable:

Parkinsonism (stiatonigral degeneration, MSA-P).
Ataxia (olivo-ponto-cerebellar degeneration, MSA-C).
Autonomic dysfunction (Shy-Drager syndrome, depreceated).
Clinical onset between 40-60 years.
Progedient tremor, atxia, laryngeal paresis, wakness, cognitive decline.
Patients usually succumb after 6 years from aspiration pneumonia.

DDx:

Macroscopy

Cerebral (mild) & cerebellar atrophy.
greenish putamen.
Discoloration Substantia nigra and Locus coeruleus

Microscopic

Features:

Inclusions cerebral, subcortical white matter, cerebellar.
Neuronal loss and gliosis.
Alpha-synuclein-rich glial and neuronal cytoplasmic inclusions (finding at autopsy).^[45]
- Inclusions in oligodendrocytes.^[46]
Pons and Putamen:
- Nuclear inclusions (sparse in most cases).
- Neuropil threads (alpha-synuclein).
Loss of myelinated fibers from external capsule, striatum and pallidum.

Images

Gray-brown discoloration in putamen of a striatonigral-type MSA (WC/jensflorian).
Gallays silver stain showing MSA-typic inclusions (WC/jensflorian).
a-synuclein IHC showing Glial and neuronal cytoplasmic inclusion in the pons of a MSA case (WC/jensflorian).

Molecular

No known alpha-synuclein mutation.
Genetic variants of SNCA gene assoicated with MSA. ^[47]

Tauopathies

Progressive supranuclear palsy

Commonly abbreviated PSP.
AKA Steele-Richardson-Olszewski syndrome.

General

Diagnosis - clinical.^[48]

Clinical:

Impaired control of gaze, esp. difficulty looking up and down (supranuclear palsy).^[49]
Parkinsonism.^[11]

Microscopic

Features:^[1]^[48]^[50]

Globose neurofibrillary tangles in neurons.
Coiled bodies in oligodendrocytes.
- Wire coil-like structure around the nucleus.
Tufted astrocytes.
- Near impossible to see without IHC - specifically AT8.
- Cellular processes filled with crap.
- Star-like appearance; looks like a road network where all the roads lead to one place (Parisian star).
Grumose degeneration of the cerebellar dentate nucleus.
- Granular eosinophilic material adjacent to nuclei; once thought to be pathognomonic for PSP.^[51]^[52]

Images:

PSP - several images (upmc.edu).

Pick disease

General

Dementia.

Gross

Frontal and temporal lobe atrophy.^[53]
- May be called "walnut brain"^[54] - as it resembles a walnut.

Microscopic

Features:^[53]

Pick cells = large ballooned neurons.
Pick bodies = round, homogenous, intracytoplasmic inclusions, size ~10 micrometers.

Image(s):

Pick body (nature.com).^[55]

Other

Chronic traumatic encephalopathy

Abbreviated CTE.

Main article: Chronic traumatic encephalopathy

Huntington disease

General

Autosomal dominant inheritance.
Mutation in Huntington gene (HTT):^[56]
- 11-34 CAG repeat = normal.^[57]
- >42 CAG repeat = Huntington disease.

Clinical:^[58]

Early onset dementia.
Involuntary movements (chorea) - both arms and legs.
Behaviour changes, e.g. grimacing.
Speech changes.

Gross

Severe caudate atrophy.^[59]
- Prominent frontal horns of the lateral ventricles.^[60]

Note:

A normal caudate bulges into the ventricle.

Images:

Microscopic

Features:^[58]

Neuron loss.
Gliosis.

Binswanger 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.

Frontotemporal lobar degeneration with ubiquitinated inclusions

Abbreviated FTLD with ubiquitinated inclusions or FTLD-TDP43.

General

There are several forms of frontotemporal dementia.
Related to amyotrophic lateral sclerosis (ALS); also a TDP-43 pathology.^[61]
- There are several subtypes of FTLD with TDP-43.

Gross

Frontal and temporal lobe atrophy.

Image:

FTLD (WC).

Amyotrophic lateral sclerosis

Abbreviated ALS.

General

AKA Lou Gehrig's disease.
TDP-43 proteinopathy.
Characterized by motor neuron death.
May be familial and associated with SOD1 gene.^[62]

Clinical:

Weakness.

Microscopic

Features:^[62]

Motor neurons with Bunina bodies.
- PAS positive cytoplasmic inclusions.
Motor neuron loss + reactive gliosis + neurogenic muscular atrophy.

Images:

Hallervorden-Spatz disease

AKA pantothenate kinase-associated neurodegeneration.

General

Uncommon.

Microscopic

Features:^[64]

Axonal spheroids.
Iron deposition.

Images:

HSD - several images (upmc.edu).

Stains

Prussian blue +ve.

References

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↑ Online 'Mendelian Inheritance in Man' (OMIM) 602544
↑ ^44.0 ^44.1 Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1319. ISBN 978-1416031215.
↑ 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.
↑ MUN. 16 November 2010.
↑ Pimenta, PF.; da Silva, RP.; Sacks, DL.; da Silva, PP. (Apr 1989). "Cell surface nanoanatomy of Leishmania major as revealed by fracture-flip. A surface meshwork of 44 nm fusiform filaments identifies infective developmental stage promastigotes.". Eur J Cell Biol 48 (2): 180-90. PMID 2743996.
↑ ^48.0 ^48.1 URL: http://emedicine.medscape.com/article/1151430-overview. Accessed on: 11 November 2010.
↑ Levy, R. (Jun 2011). "[Progressive supranuclear palsy: what's new?].". Geriatr Psychol Neuropsychiatr Vieil 9 (2): 191-201. doi:10.1684/pnv.2011.0271. PMID 21690028.
↑ 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.
↑ URL: http://neuropathologyblog.blogspot.com/2008/03/grumose-degeneration-in-cerebellar.html. Accessed on: 4 December 2010.
↑ Yamanouchi H, Yokoo H, Yuhara Y, et al. (March 2002). "An autopsy case of ornithine transcarbamylase deficiency". Brain Dev. 24 (2): 91–4. PMID 11891099.
↑ ^53.0 ^53.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 676. ISBN 978-1416054542.
↑ URL: http://medical-dictionary.thefreedictionary.com/Walnut+Brain. Accessed on: 14 March 2012.
↑ Grossman, M. (Feb 2010). "Primary progressive aphasia: clinicopathological correlations.". Nat Rev Neurol 6 (2): 88-97. doi:10.1038/nrneurol.2009.216. PMID 20139998.
↑ Kumar P, Kalonia H, Kumar A (2010). "Huntington's disease: pathogenesis to animal models". Pharmacol Rep 62 (1): 1–14. PMID 20360611.
↑ Online 'Mendelian Inheritance in Man' (OMIM) 613004
↑ ^58.0 ^58.1 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 415 Q44. ISBN 978-1416025887.
↑ URL: http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm. Accessed on: 29 October 2010.
↑ URL: http://path.upmc.edu/cases/case117/gross.html. Accessed on: 3 January 2012.
↑ Online 'Mendelian Inheritance in Man' (OMIM) 105400
↑ ^62.0 ^62.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 679. ISBN 978-1416054542.
↑ URL: http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm. Accessed on: 30 August 2011.
↑ URL: http://path.upmc.edu/cases/case207/dx.html. Accessed on: 11 January 2012.

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[pmid25917706-14] Korczyn, AD. (Apr 2015). "Vascular parkinsonism-characteristics, pathogenesis and treatment.". Nat Rev Neurol. doi:10.1038/nrneurol.2015.61. PMID 25917706.

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[omim609007-42] Online 'Mendelian Inheritance in Man' (OMIM) 609007

[omim602544-43] Online 'Mendelian Inheritance in Man' (OMIM) 602544

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[omim613004-57] Online 'Mendelian Inheritance in Man' (OMIM) 613004

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@@ Line 207: / Line 207: @@
 ===Parkinsonism causes===
 *Parkinson's disease <ref name=pmid17390256>{{Cite journal  | last1 = Tuite | first1 = PJ. | last2 = Krawczewski | first2 = K. | title = Parkinsonism: a review-of-systems approach to diagnosis. | journal = Semin Neurol | volume = 27 | issue = 2 | pages = 113-22 | month = Apr | year = 2007 | doi = 10.1055/s-2007-971174 | PMID = 17390256 }}</ref>
-*Dementia with Lewy bodies.
+*[[Dementia with Lewy bodies]].
 *[[Multiple system atrophy]] (MSA).<ref name=pmid22074330>{{Cite journal  | last1 = Ahmed | first1 = Z. | last2 = Asi | first2 = YT. | last3 = Sailer | first3 = A. | last4 = Lees | first4 = AJ. | last5 = Houlden | first5 = H. | last6 = Revesz | first6 = T. | last7 = Holton | first7 = JL. | title = Review: The neuropathology, pathophysiology and genetics of multiple system atrophy. | journal = Neuropathol Appl Neurobiol | volume =  | issue =  | pages =  | month = Nov | year = 2011 | doi = 10.1111/j.1365-2990.2011.01234.x | PMID = 22074330 }}</ref>
 *[[Progressive supranuclear palsy]] (PSP).<ref name=pmid22228724>{{Cite journal  | last1 = Bertram | first1 = K. | last2 = Williams | first2 = DR. | title = Visual hallucinations in the differential diagnosis of parkinsonism. | journal = J Neurol Neurosurg Psychiatry | volume = 83 | issue = 4 | pages = 448-52 | month = Apr | year = 2012 | doi = 10.1136/jnnp-2011-300980 | PMID = 22228724 }}</ref>
-*Drug induced (valproic acid).<ref name=pmid21993183>{{Cite journal  | last1 = Mahmoud | first1 = F. | last2 = Tampi | first2 = RR. | title = Valproic Acid-Induced Parkinsonism in the Elderly: A Comprehensive Review of the Literature. | journal = Am J Geriatr Pharmacother | volume =  | issue =  | pages =  | month = Oct | year = 2011 | doi = 10.1016/j.amjopharm.2011.09.002 | PMID = 21993183 }}</ref>
+*Drug induced (valproic acid, MPTP).<ref name=pmid21993183>{{Cite journal  | last1 = Mahmoud | first1 = F. | last2 = Tampi | first2 = RR. | title = Valproic Acid-Induced Parkinsonism in the Elderly: A Comprehensive Review of the Literature. | journal = Am J Geriatr Pharmacother | volume =  | issue =  | pages =  | month = Oct | year = 2011 | doi = 10.1016/j.amjopharm.2011.09.002 | PMID = 21993183 }}</ref><ref name=pmid1815982> {{Cite journal  | last1 = Gerlach | first1 = M. | last2 = Riederer | first2 = P. | last3 = Przuntek | first3 = H. | last4 = Youdim | first4 = MB. | title = MPTP mechanisms of neurotoxicity and their implications for Parkinson's disease. | journal = Eur J Pharmacol | volume = 208 | issue = 4 | pages = 273-86 | month = Dec | year = 1991 | doi =  | PMID = 1815982 }}</ref>
+* Vascular. <ref name=pmid25917706>{{Cite journal  | last1 = Korczyn | first1 = AD. | title = Vascular parkinsonism-characteristics, pathogenesis and treatment. | journal = Nat Rev Neurol | volume =  | issue =  | pages =  | month = Apr | year = 2015 | doi = 10.1038/nrneurol.2015.61 | PMID = 25917706 }}</ref>
+* Postencephalitic. <ref name=pmid20629120>{{Cite journal  | last1 = Vilensky | first1 = JA. | last2 = Gilman | first2 = S. | last3 = McCall | first3 = S. | title = A historical analysis of the relationship between encephalitis lethargica and postencephalitic parkinsonism: a complex rather than a direct relationship. | journal = Mov Disord | volume = 25 | issue = 9 | pages = 1116-23 | month = Jul | year = 2010 | doi = 10.1002/mds.22908 | PMID = 20629120 }}</ref>
+* Tramuatic (Dementia pugilistica).<ref name=pmid24398724>{{Cite journal  | last1 = Chauhan | first1 = NB. | title = Chronic neurodegenerative consequences of traumatic brain injury. | journal = Restor Neurol Neurosci | volume = 32 | issue = 2 | pages = 337-65 | month =  | year = 2014 | doi = 10.3233/RNN-130354 | PMID = 24398724 }}</ref>
 =Amyloidoses=
@@ Line 381: / Line 384: @@
 =Alpha-synucleinopathies=
-Includes the Lewy body diseases [[Parkinson's disease]] and [[Dementia with Lewy bodies]].
+Without clincial information [[Parkinson's disease]] and [[Dementia with Lewy bodies]] cannot separated in histology.
 ==Dementia with Lewy bodies==
@@ Line 393: / Line 396: @@
 Features:
 *[[Lewy bodies]].
+*Lewy neurites.
+Note: Cortical Lewy bodies are easily missed in HE.
 ===IHC===
 *Alpha-synuclein +ve.
+===Images===
+<gallery>
+File:DLB frontal lewy bodies HE.jpg | Lewy bodies in frontal cortex of DLB. (WC/jensflorian)
+File:A synuclein cortex DLB.jpg | Alpha-synculein IHC showing cortical Lewy bodies. (WC/jensflorian)
+File:Lewy neurites alpha synuclein.jpg | Alpha-synculein IHC showing Lewy Neurites in DLB. (WC/jensflorian)
+</gallery>
 ==Parkinson disease==
@@ Line 430: / Line 442: @@
 ***Consist of filaments composed of alpha-synuclein.
 *Lewy neurites - alpha-synuclein positive processes.
 ===IHC===
 *Alpha-synuclein +ve.
@@ Line 435: / Line 448: @@
 ===Images===
 <gallery>
+File:Journal.pone.0008247.g001.png | Schematic progression of PD (PLOSone/Jubault et al.).
 File:Histological sample of Substantia nigra in Parkinson's disease.jpg | Lewy body (HE, left) and Lewy neurite (aSyn IHC, right).
 File:Lewy Body alphaSynuclein.jpg | Alpha-synculein positive Lewy body (WC/Marvin101).
 File:Lewy bodies (alpha synuclein inclusions).jpg | Lewy body and Lewy neurites (WC/Suraj Rajan).
 </gallery>
+===Molecular===
+*Hereditary forms in less than 10% of the cases
+**Involved genes are consecutively labeled PARK1, PARK2....
 ==Multiple system atrophy==

Difference between revisions of "Neurodegenerative diseases"

Revision as of 08:34, 7 May 2015

Overview

Common diseases

Table

Immunohistochemistry

Alpha-synuclein

Tau

TDP-43

Microscopic

Ubiquitin

Microscopic

Clinical perspective

Dementia general (mostly useless) DDx

Mnemonic

Functional anatomy of dementia

Parkinsonism causes

Amyloidoses

Alzheimer disease

General

Genetics

Gross

Images

Microscopic

Images

Classification

Prion diseases

General

IHC

Creutzfeldt-Jakob disease

General

Variant Creutzfeldt-Jakob disease

General

Microscopic

Images

Alpha-synucleinopathies

Dementia with Lewy bodies

General

Microscopic

IHC

Images

Parkinson disease

General

Gross

Microscopic

IHC

Images

Molecular

Multiple system atrophy

General

Macroscopy

Microscopic

Images

Molecular

Tauopathies

Progressive supranuclear palsy

General

Microscopic

Pick disease

General

Gross

Microscopic

Other

Chronic traumatic encephalopathy

Huntington disease

General

Gross

Microscopic

Binswanger disease

General

Microscopic

Frontotemporal lobar degeneration with ubiquitinated inclusions

General

Gross

Amyotrophic lateral sclerosis

General

Microscopic

Hallervorden-Spatz disease

General

Microscopic