raclopride and Supranuclear-Palsy--Progressive

Progressive supranuclear palsy (PSP) is a clinicopathological syndrome related to tau deposits and in linkage disequilibrium with tau polymorphisms. Some rare familial PSP cases have been related to tau gene mutations.. To present the clinical, pathological, and molecular data of one family with early-onset autosomal dominant PSP.. We performed clinical examinations, quantitative neurological tests, positron emission tomographic scans with fluorodopa F 18 and raclopride C 11, analysis of tau mutations, neuropathological examinations, and protein analyses on brain specimens.. Three family members had PSP confirmed by pathological features in the proband. A novel mutation of tau, G303V, was found in the proband and other family members. tau Isoforms with 4 microtubule-binding repeats were overexpressed in the proband brain.. The G303V mutation of tau is associated with autosomal dominant PSP. Expression of 4 microtubule-binding repeat tau isoforms is increased in the proband.

Topics: Amino Acid Substitution; Blotting, Northern; Blotting, Western; Brain; Dihydroxyphenylalanine; DNA Mutational Analysis; Family Health; Female; Genetic Predisposition to Disease; Glycine; Humans; Immunohistochemistry; Middle Aged; Mutation; Neurologic Examination; Positron-Emission Tomography; Protein Isoforms; Raclopride; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Supranuclear Palsy, Progressive; tau Proteins; Valine

Equilibrium striatal: cerebellar 11C-raclopride (RAC) uptake ratios reflect the density of striatal dopamine D2 binding sites. Using positron emission tomographic scanning we have measured striatal RAC uptake in 6 untreated patients with Parkinson's disease (PD), 5 chronically treated patients with PD and a fluctuating response to L-dopa, 10 patients with striatonigral degeneration (SND), and 9 patients with progressive supranuclear palsy (PSP). Regional cerebral blood flow was determined also, with C15O2. Mean striatal: cerebellar RAC uptake was not significantly different from normal in untreated patients with PD, though 2 of these 6 patients showed significantly increased putamen tracer binding. Mean caudate and putamen: cerebellar RAC uptake ratios of the group with PD and a fluctuating response to L-dopa were significantly reduced by 30% and 18%, respectively. The patients with SND had lesser, but significant, 10% and 11% decreases in mean caudate and putamen: cerebellar RAC uptake ratios, respectively, whereas patients with PSP showed 24% and 9% reductions in caudate and putamen: cerebellar RAC binding. Striatal and frontal blood flow were significantly reduced in patients with PSP, but not in patients with PD or SND. In conclusion, striatal D2 binding potential is normal or raised in untreated patients with PD, but reduced in patients with PD and a fluctuating response to L-dopa. Patients with SND and PSP show a decrease in striatal RAC binding, but to a lesser extent than patients with PD and a fluctuating response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Caudate Nucleus; Corpus Striatum; Humans; Levodopa; Middle Aged; Nerve Degeneration; Parkinson Disease; Putamen; Raclopride; Receptors, Dopamine; Salicylamides; Substantia Nigra; Supranuclear Palsy, Progressive; Tomography, Emission-Computed