To verify our hypothesis of defective
protease inhibitor domains that are encoded by abnormal processing of
amyloid precursor
protein (APP) in brains of patients with
neuronal ceroid lipofuscinoses (NCL), immunohistochemical and cytochemical studies were performed with
monoclonal antibodies (mAbs) directed against various domains of APP. For the studies, 22 autopsy brains were used: 12 with different forms of NCL, and 10 control brains. The staining procedure for the
avidin-
biotin complex (ABC) technique and the postembedding
gold-labelled procedure for electron microscopy (EM) were employed. Of all mAbs used for the study, only mAbs generated against
amyloid B-
protein bound to neural tissue were affected with NCL. The strongest immunostaining of neurons and of some reactive glial cells was found in brains with the juvenile form of NCL. Only in the infantile form of the disease were some neurons overloaded with storage material weakly immunoreactive. In brains of patients with the adult form of NCL, immunoreactivity was found in affected neurons and in extracellularly deposited material of
senile plaques. The results of EM study showed that the immunoreactivity was restricted to lysosomal cytosomes in neural tissue with any form of NCL selectively localized on the curvilinear and fingerprint proteinaceous component of
ceroid lipofuscin. Studies performed on control aging brains and
Alzheimer's disease (AD) brains confirmed previous observations of immunoreactivity being found diffusely in the
protein component of some neurons containing
lipopigment.(ABSTRACT TRUNCATED AT 250 WORDS)