Lack of regional selectivity during the progression of Parkinson disease: implications for pathogenesis.
BACKGROUND
Dopamine terminal loss in the putamen of patients with Parkinson disease (PD) shows a regional heterogeneity, reflecting selective vulnerability of degenerating neurons to mechanisms of cell death.


OBJECTIVE
If the same pathogenic mechanisms are responsible for the onset and progression of PD, the regional selectivity of dopamine cell loss will be the same throughout the course of the disorder.


OBJECTIVE
To investigate the regional selectivity of dopamine terminal loss during the progression of PD.


METHODS
We studied 67 patients with PD and 20 healthy subjects using positron emission tomography with [(11)C](+/-)dihydrotetrabenazine (DTBZ).


RESULTS
Regional values of DTBZ binding potential (calculated as maximum specific binding [B(max)] divided by the equilibrium dissociation constant K(d)) against disease duration in the putamen of PD patients were best described by a multivariate exponential model with distinct parallel asymptotic values that were significantly (P<.001) different across 4 regions of the putamen. The extent of loss of DTBZ binding potential with disease progression during the clinical stage of PD (early vs late PD) was similar between the anterior (-33%, using early PD as the baseline) and posterior (-29%) putamen. In contrast, the extent of loss of DTBZ binding potential in early PD, which reflects the cumulated loss of DTBZ binding potential from the onset of the disorder (in healthy subjects vs those with early PD), was significantly (P<.001) lower in the posterior (-58%, using healthy subjects as the baseline) than the anterior (-42%) putamen.


CONCLUSIONS
To the extent that DTBZ positron emission tomography provides an accurate estimate of loss of dopamine neurons, our findings suggest that the mechanisms responsible for the progression of PD may not be the same as those responsible for its onset.
Lee
Chong S
CS
Pacific Parkinson's Research Centre, Vancouver Hospital & Health Sciences Centre, 2221 Wesbrook Mall, Purdy Pavilion Room M36, Vancouver, British Columbia, Canada V6T 2B5. cslee@interchange.ubc.ca
Schulzer
Michael
M
de la Fuente-Fernández
Raúl
R
Mak
Edwin
E
Kuramoto
Lisa
L
Sossi
Vesna
V
Ruth
Thomas J
TJ
Calne
Donald B
DB
Stoessl
A Jon
AJ
D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D012044:Regression Analysis; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism
C032811:dihydrotetrabenazine; D004298:Dopamine; D013747:Tetrabenazine