PMID- 37322038
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230619
IS  - 2373-8057 (Print)
IS  - 2373-8057 (Electronic)
IS  - 2373-8057 (Linking)
VI  - 9
IP  - 1
DP  - 2023 Jun 15
TI  - Dopamine and vesicular monoamine transport loss supports incidental Lewy body 
      disease as preclinical idiopathic Parkinson.
PG  - 89
LID - 10.1038/s41531-023-00514-z [doi]
LID - 89
AB  - Incidental Lewy body disease (ILBD) is a neuropathological diagnosis of brains 
      with Lewy bodies without clinical neuropsychiatric symptoms. Dopaminergic 
      deficits suggest a relationship to preclinical Parkinson's disease (PD). We now 
      report a subregional pattern of striatal dopamine loss in ILBD cases, with 
      dopamine found significantly decreased in the putamen (-52%) and only to a lower 
      extent in the caudate (-38%, not statistically significant); this is similar to 
      the pattern in idiopathic PD in various neurochemical and in vivo imaging 
      studies. We aimed to find out if our recently reported impaired storage of 
      dopamine in striatal synaptic vesicles prepared from striatal tissue of cases 
      with idiopathic PD might be an early or even causative event. We undertook 
      parallel measurements of [(3)H]dopamine uptake and vesicular monoamine 
      transporter (VMAT)2 binding sites by the specific label 
      [(3)H]dihydrotetrabenazine on vesicular preparation from caudate and putamen in 
      ILBD. Neither specific uptake of dopamine and binding of 
      [(3)H]dihydrotetrabenazine, nor mean values of the calculated ratios of dopamine 
      uptake and VMAT2 binding, a measure of uptake rate per transport site, were 
      significantly different between ILBD and controls. ATP-dependence of 
      [(3)H]dopamine uptake revealed significantly higher rates in putamen than in 
      caudate at saturating concentrations of ATP in controls, a subregional difference 
      lost in ILBD. Our findings support a loss of the normally higher VMAT2 activity 
      in putamen as a contributing factor to the higher susceptibility of the putamen 
      to dopamine depletion in idiopathic PD. Moreover, we suggest ILBD postmortem 
      tissue as a valuable source for testing hypotheses on processes in idiopathic PD.
CI  - (c) 2023. The Author(s).
FAU - Pifl, Christian
AU  - Pifl C
AUID- ORCID: 0000-0003-1456-4264
AD  - Center for Brain Research, Medical University of Vienna, Vienna, Austria. 
      christian.pifl@gmail.com.
FAU - Reither, Harald
AU  - Reither H
AD  - Center for Brain Research, Medical University of Vienna, Vienna, Austria.
FAU - Attems, Johannes
AU  - Attems J
AD  - Translational and Clinical Research Institute, Newcastle University, Newcastle 
      upon Tyne, UK.
FAU - Zecca, Luigi
AU  - Zecca L
AUID- ORCID: 0000-0002-7409-6653
AD  - Institute of Biomedical Technologies, National Research Council of Italy, 
      Segrate, Milan, Italy.
LA  - eng
PT  - Journal Article
DEP - 20230615
PL  - United States
TA  - NPJ Parkinsons Dis
JT  - NPJ Parkinson's disease
JID - 101675390
PMC - PMC10272141
COIS- The authors declare no competing interests.
EDAT- 2023/06/16 01:08
MHDA- 2023/06/16 01:09
PMCR- 2023/06/15
CRDT- 2023/06/15 23:18
PHST- 2022/12/08 00:00 [received]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/06/16 01:09 [medline]
PHST- 2023/06/16 01:08 [pubmed]
PHST- 2023/06/15 23:18 [entrez]
PHST- 2023/06/15 00:00 [pmc-release]
AID - 10.1038/s41531-023-00514-z [pii]
AID - 514 [pii]
AID - 10.1038/s41531-023-00514-z [doi]
PST - epublish
SO  - NPJ Parkinsons Dis. 2023 Jun 15;9(1):89. doi: 10.1038/s41531-023-00514-z.