Hot Topic Tutorial in Neurologist

Pathogenesis of Parkinsons disease

Surat Tanprawate, MD, MSc(Lond.), FRCP(T) Division of Neurology, Chiang Mai University
18.7.2012
Wednesday, July 18, 2012

Idiopathic Parkinsons disease

Second most common neurodegenerative disorder 70-80% of parkinsonism Sporadic (approx. 90%) Inherited (less than 10%) autosomal dominant autosomal recessive

Wednesday, July 18, 2012

Idiopathic Parkinsons disease

Adult onset PD Young Onset Parkinsons Disease

(YOPD)

Juvenile Parkinsonism Juvenile Parkinson disease

Wednesday, July 18, 2012

Historical note

Tretiakoff (1919)

examined the brains of nine parkinsonian patients substantia nigra lesions were important in both Parkinsons disease and in postencephalitis patient

Friedrich Lewy (1912) They (intracellular inclusions) are simply nding which i up till now have found in all cases of paralysis agitans that i have examined, but which were absent in the other (control) cases

Wednesday, July 18, 2012

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 sunower with a dense central core of circular shaped structures and a rim of radiating laments
Wednesday, July 18, 2012

Parkinsons disease
Microscopic 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, parasympathetic neurons

Wednesday, July 18, 2012

Pale bodies Abnormal neurites

Wednesday, July 18, 2012

Wednesday, July 18, 2012

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

Wednesday, July 18, 2012

PD- diagnostic criteria

Diagnostic accuracy to 82%

Wednesday, July 18, 2012

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

Wednesday, July 18, 2012

Braak staging of PD

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

Wednesday, July 18, 2012

Etiology
Genetic Twin study, 1st degree relative Environmental factors rural area organophosphate Animal model: pyrethione pesticide
Wednesday, July 18, 2012

Pathophysiology of PD
Wednesday, July 18, 2012

Lancet 2006; 368: 7082

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

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Mitochondrial etiology and Parkinsons disease

Wednesday, July 18, 2012

Mitochondrial etiology and PD

First recognized in 1989

defect of respiratory chain complex I was identied in SN

Discovery complex I deciency in PD Genetic encode mitochondrial protein mutation; PINK 1, DJ1= AR of PD

Wednesday, July 18, 2012

Mitochondrial abnormal associated with alphasynnuclein and Parkin expression

Environmental toxin (MPTP): caused mitochondrial inhibiter of complex I

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

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

Wednesday, July 18, 2012

END

Wednesday, July 18, 2012