the pathogenesis of pd

7/31/2019 The Pathogenesis of PD

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Pathogenesis ofParkinsons disease

Surat Tanprawate, MD, MSc(Lond.), FRCP(T)Division of Neurology, Chiang Mai University

Hot Topic Tutorial in Neurologist

18.7.2012

Wednesday, July 18, 2012


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Idiopathic Parkinsons disease

Second most commonneurodegenerativedisorder

70-80% of parkinsonism

Sporadic

(approx. 90%)

Inherited

(less than 10%)

autosomal dominant

autosomal recessive



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Idiopathic Parkinsons

disease Adult onset PD

Young Onset Parkinsons Disease(YOPD)

Juvenile Parkinsonism Juvenile Parkinson disease



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Historical note

Tretiakoff (1919)

examined the brains of nine parkinsonian patients

substantia nigra lesions were important in bothParkinsons disease and in postencephalitis patient

Friedrich Lewy (1912)

They (intracellular inclusions) are simply findingwhich i up till now have found in all cases of paralysis

agitans that i have examined, but which were absentin the other (control) cases



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Lewy bodies

Lewy bodies are circular eosinophilic

structures with a dense protein core

surrounded by a peripheral halo

located within the cytoplasm of

neurons.

The ultrastructural appearance is like a sunflower with

a dense central core of circular shaped structures and

a rim of radiating filamentsWednesday, July 18, 2012


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Parkinsons diseaseMicroscopic Pathology:

Cell loss

Substantia nigra (50% loss)

Locus coeruleus

Lewy bodies (8-30m, intracytoplasmic,

neuronal inclusions)# Substantia nigra

# locus coeruleus and raphe

# IX & X cranial nerve nuclei

# Mesocorticolimbic system

# Meynert nucleus

Cortex# Intermediolateral column of the cord

# Sympathetic, parasympatheticneurons

Pale bodies

Abnormal neurites



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Gibb et al, 1988, Table from Litvan et al, 2003



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H. Braak et al. / Neurobiology of Aging 24 (2003) 197211

Braak staging of PD



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Etiology

Genetic

Twin study, 1st degree relative

Environmental factors

rural area

organophosphate

Animal model: pyrethione pesticide



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Lancet2006; 368: 7082

Pathophysiology of PDWednesday, July 18, 2012


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Human Molecular Genetics, 2005, Vol. 14, No. 27492755



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Mitochondrial etiology and

Parkinsons disease



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Mitochondrial etiology and

PD First recognized in 1989

defect of respiratory chain complex I was identified in

SN

Discovery complex I deficiency in PD

Genetic encode mitochondrial protein mutation; PINK 1,DJ1= AR of PD

Mitochondrial abnormal associated with alpha-

synnuclein and Parkin expression

Environmental toxin (MPTP): caused mitochondrial

inhibiter of complex I



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Human Molecular Genetics, 2005, Vol. 14, No. 27492755



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the pathogenesis of pd

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