COMPARISON OF CATHEPSIN PROTEASE ACTIVITIES IN BRAIN-TISSUE FROM NORMAL CASES AND CASES WITH ALZHEIMERS-DISEASE, LEWY BODY DEMENTIA, PARKINSONS-DISEASE AND HUNTINGTONS-DISEASE

Recent evidence, based upon immunocytochemical and histochemical analy sis of brain cortical tissue from Alzheimer's disease patients, has su ggested that altered activity and/or distribution of the lysosomal pro teases cathepsins B and D may be implicated in the abnormal protein pr ocessing pathway resulting in formation of the neurotoxic amyloid A4 p eptide, characteristic of this neurodegenerative disorder. We have the refore compared, via biochemical assay techniques using conventional o r specially synthesised (corresponding to protein cleavage points of r elevant to A4 peptide formation) fluorogenic substrates, the levels of activity of the lysosomal proteases cathepsins B, D, H and L, and dip eptidyl aminopeptidases I and II in frontal cortex (grey/white matter) from control and Alzheimer's disease patients. For comparative purpos es, activity levels of the above enzymes were also determined in front al cortex tissue from cases with Lewy body dementia and Parkinson's di sease, and in caudate tissue from control and Huntington's disease cas es. There was no significant difference in activity for any protease t ypes in tissue from control cases and cases with Alzheimer's disease, Lewy body dementia or Parkinson's disease, with the exception of reduc ed dipeptidyl aminopeptidase II activity in Lewy body dementia and Par kinson's cases. We have therefore been unable to confirm a potential r ole for lysosomal cathepsins in the characteristic neurodegeneration a ssociated with Alzheimer's disease; however the finding of significant increases in activity of dipeptidyl aminopeptidase II, cathepsin H an d cathepsin D specifically in cases with Huntington's disease is of pa rticular note. We therefore suggest the potential role of the latter e nzymes in the pathogenesis of Huntington's disease requires further in vestigation.