Cholinergic vesicular transporters in progressive supranuclear palsy.
OBJECTIVE
To determine the status of cholinergic and monoaminergic vesicular transporter binding sites in progressive supranuclear palsy (PSP).


METHODS
The authors determined autoradiographically the regional expression of acetylcholine vesicular transporter (VAChT) and monoamine vesicular transporter type 2 (VMAT2) binding sites in postmortem basal ganglia samples from subjects with PSP. Comparison neurochemical measures included choline acetyltransferase (ChAT) enzyme activity and benzodiazepine (BZ) binding sites.


RESULTS
VAChT expressions and ChAT activities in caudate nucleus and putamen were markedly decreased in PSP, whereas BZ binding was unaffected, consistent with selective losses of striatal cholinergic interneurons. VMAT2 density was reduced significantly in the caudate nucleus, putamen, and substantia nigra pars compacta, consistent with degeneration of dopaminergic nigrostriatal projection neurons in PSP. In the globus pallidus, BZ receptor binding sites were reduced, whereas VMAT2 and VAChT binding sites were unchanged, indicating losses of intrinsic pallidal neurons and synapses.


CONCLUSIONS
These results confirm selective and marked degenerations of basal ganglia cholinergic and dopaminergic terminals in PSP. Striatal VAChT reduction may provide a unique neurochemical imaging marker for distinction of PSP from other types of basal ganglia neurodegeneration.
Suzuki
Masahiko
M
Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, USA.
Desmond
Timothy J
TJ
Albin
Roger L
RL
Frey
Kirk A
KA
D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000378:metabolism; D015415:Biomarkers / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009479:Neuropeptides; D011963:Receptors, GABA-A / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins
D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D011963:Receptors, GABA-A; C493452:SLC18A2 protein, human; C493459:SLC18A3 protein, human; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine