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. 2006 Apr 5;12(4):430–441. doi: 10.1111/j.1750-3639.2002.tb00460.x

Caspase‐cleaved Amyloid Precursor Protein in Alzheimer's Disease

Carlos Ayala‐Grosso 1, Gordon Ng 2, Sophie Roy 3, George S Robertson 2,✉
PMCID: PMC8095892  PMID: 12408229

Abstract

Caspase‐3 mediated cleavage of the amyloid precursor protein (APP) has been proposed as a putative mechanism underlying amyloidosis and neuronal cell death in Alzheimer's disease (AD). We utilized an antibody that selectively recognizes the neo epitope generated by caspase‐3 mediated cleavage of APP (αΔCcsp‐APP) to determine if this proteolytic event occurs in senile plaques in the inferior frontal gyrus and superior temporal gyrus of autopsied AD and age‐matched control brains. Consistent with a role for caspase‐3 activation in AD pathology, αΔCcsp‐APP immunoreactivity colocalized with a subset of TUNEL‐positive pyramidal neurons in AD brains. αΔCcsp‐APP immunoreactivity was found in neurons and glial cells, as well as in small‐and medium‐size particulate elements, resembling dystrophic terminals and condensed nuclei, respectively, in AD and age‐matched control brains. There were a larger number of αΔCcsp‐APP immunoreactive elements in the inferior frontal gyrus and superior temporal gyrus of subjects with AD pathology than age‐matched controls. αΔCcsp‐APP immunoreactivity in small and medium size particulate elements were the main component colocalized with 30% of senile plaques in the inferior frontal gyrus and superior temporal gyrus of AD brains. In some control brains, αΔCcsp‐APP immunoreactivity appeared to be associated with a clinical history of metabolic encephalopathy. Our results suggest that apoptosis contributes to cell death resulting from amyloidosis and plaque deposition in AD.

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