Thesubstantia nigra andventral tegmental areain Alzheimer's disease andDown'ssyndrome
1989
SUMMARY Degenerative changes inthesubstantia nigra andventral tegmental areawere investigated in104casesofAlzheimer's disease and13casesofDown'ssyndrome. Frequencies oftangles inthree groupsofpatients withAlzheimer's disease were 86%,44% and46% (54%overall) respectively. Abouthalf ofthose withtangles, butno Lewybodies, hadexcessnigral cell loss, and 16%hadmoderate or severeneuronal fallout, butnone hadaParkinsonian syndrome. Caseswith nigral tangles wereyounger,tended tohave more hippocampal andcortical tangles andplaques, and lower activities ofcortical choline acetyltransferase. InmostcasesofAlzheimer's disease degeneration innigral andtegmental areaswas greater thancontrols, andtangles wereevenly distributed. All thecasesofDown'ssyndrome hadtangles inthenigra andeight showedmildcell loss. Mild degenerative changes accompanied bytangles inthesubstantia nigra andventral tegmental areaare common inAlzheimer's disease, butseverecell loss is rare.WhenaParkinsonian syndrome occursin Alzheimer's disease itislikely tobeduetoLewybodypathology. InAlzheimer's disease (AD)neuronal lossand neurofibrillary tangle formation occur inthelocus coeruleus'" andraphe nuclei.56 Incontrast, neuronal loss andtangle formation inthesubstantia nigra issaid tobeuncommmon, andwhenpresent tangles are confined tothemedial substantia nigra.7 A recent review stated that tangles inthesubstantia nigra were rareinAD,butLewybodies werefound inafew cases.8 Theventral tegmental areawassaid toshow moderately frequent neurofibrillary tangles. There are noquantitative studies comparing thefrequency and distribution ofneurofibrillary tangles inthesubstantia nigra andventral tegmentum inAD,norhastheextent ofcell damage beenclearly documented. Reduction of dopamine levels incaudate nucleus andputamen"' suggest thatnigral cell loss maybemoreextensive in AD thangenerally recognised. Ithasalso beensuggested that somepatients with Parkinsonian syndromes ofunknowncausehave nigral degeneration withtangles,'2 representing either cases ofprevious encephalitis lethargica withsub
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