The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases.
BACKGROUND
Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder involving motor and cognitive dysfunction. Currently, there is no effective treatment either for symptomatic relief or disease modification. This relates, in part, to a lack of knowledge of the underlying neurochemical abnormalities, including cholinergic receptor status in the basal ganglia.


OBJECTIVE
To measure muscarinic M2 and M4 receptors in the basal ganglia in PSP.


METHODS
The muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum, pallidum and adjacent insular cortex were autoradiographically measured in pathologically confirmed cases of PSP (n = 18), and compared with cases of Lewy body dementias (LBDs; n = 45), Alzheimer's disease (AD; n = 39) and controls (n = 50).


RESULTS
In cases of PSP, there was a reduction in M2 and M4 receptors in the posterior caudate and putamen compared to controls, but no significant changes in the pallidum. Cases with AD showed lower M2 receptors in the posterior striatum. Groups with LBD and AD showed higher M2 binding in the insular cortex compared with controls.


CONCLUSIONS
The results suggest loss of posterior striatal cholinergic interneurones in PSP, and reduction in medium spiny projection neurones bearing M4 receptors. These results should be taken in the context of more widespread pathology in PSP, but may have implications for future trials of cholinergic treatments.
Warren
N M
NM
Institute for Ageing and Health, Newcastle University, New Castle upon Tyne, UK. naomiwarren@doctors.org.uk
Piggott
M A
MA
Lees
A J
AJ
Burn
D J
DJ
D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology; D043585:Receptor, Muscarinic M2 / Q000032:analysis*; D043588:Receptor, Muscarinic M4 / Q000032:analysis*; D011950:Receptors, Cholinergic / Q000032:analysis; D013494:Supranuclear Palsy, Progressive / Q000473:pathology*
D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D011950:Receptors, Cholinergic