Incidental Lewy body disease and preclinical Parkinson disease.
BACKGROUND
The significance of Lewy bodies detected at autopsy in the brains of clinically normal individuals is uncertain but may represent preclinical Parkinson disease (PD).


OBJECTIVE
To determine whether diminished striatal dopaminergic innervation and nigral cell loss are present in incidental Lewy body disease (iLBD), as one might expect if it is a forerunner of PD.


METHODS
Case-control study.


METHODS
Medical records and archival brain tissue were obtained from a tertiary medical center for further study.


METHODS
Brains from clinically healthy individuals older than 60 years with alpha-synuclein-immunoreactive Lewy bodies (iLBD; n = 12) were compared with those from clinically healthy individuals with no alpha-synuclein pathologic findings (n = 31) and patients with PD (n = 25).


METHODS
Striatal dopaminergic integrity assessed in sections of putamen by immunofluorescence for tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2), neuronal loss score in the substantia nigra, and distribution of Lewy bodies according to PD stage.


RESULTS
Among the participants with iLBD, decreased striatal dopaminergic immunoreactivity was documented for both TH (33%) and VMAT2 (42%), compared with the pathologically normal subjects; as expected, the reductions were even greater in PD (73% decrease for TH and 96% decrease for VMAT2). Substantia nigra neuronal loss inversely correlated with both striatal TH (r = -0.84) and VMAT2 (r = -0.77). In addition, PD stage inversely correlated with both striatal VMAT2 (r = -0.85) and TH (r = -0.85).


CONCLUSIONS
The results indicate that iLBD has nigrostriatal pathological features that are intermediate between those in pathologically normal persons and those with PD. The findings suggest that iLBD probably represents presymptomatic PD, rather than nonspecific, age-related alpha-synuclein pathological changes.
DelleDonne
Anthony
A
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Klos
Kevin J
KJ
Fujishiro
Hiroshige
H
Ahmed
Zeshan
Z
Parisi
Joseph E
JE
Josephs
Keith A
KA
Frigerio
Roberta
R
Burnett
Melinda
M
Wszolek
Zbigniew K
ZK
Uitti
Ryan J
RJ
Ahlskog
J Eric
JE
Dickson
Dennis W
DW
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D033162:Incidental Findings; D020961:Lewy Body Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D015415:Biomarkers; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase