CYSTATIN A-LIKE IMMUNOREACTIVITY IS WIDELY DISTRIBUTED IN HUMAN BRAINAND ACCUMULATES IN NEURITIC PLAQUES OF ALZHEIMER-DISEASE SUBJECTS

The cellular localization of cystatin A, an endogeneously occurring in hibitor of lysosomal thiol proteases (cathepsins B, H, L and S), was s tudied immunohistochemically in human postmortem brain using the perox idase-antiperoxidase method. Both polyclonal and monoclonal antibodies to cystatin A were employed. Western blot analysis revealed one molec ular form of the inhibitor in human brain extracts. Its molecular weig ht was about 13.000. Immunostaining appeared in a sizeable population of neurons and a few cells surrounding cerebral blood vessels (pericyt es). In Alzheimer disease subjects cystatin A was found in many neurit ic plaques. Possible functional consequences with regard to a role of cystatin A in the inhibition of the Alzheimer amyloid precursor protei n (APP)-clipping enzyme, cathepsin B, are discussed.