Caspase activation in the limbic cortex of subjects with early Alzheimer's disease.
We investigated the cleavage of caspase-3, a marker of apoptosis, in the medial temporal lobe of older subjects with minimal cognitive deficits and low CERAD/intermediate Braak scores, that is, clinicopathological descriptors of early Alzheimer's disease (AD). The activation of caspase-3 was studied with immunoprecipitation-mass spectroscopy and immunocytochemistry, including colocalization with paired helical filaments in the neuropil and perikarya. We found that caspase-3 is activated in the parahippocampal gyrus in subjects with mild AD and that this event is silenced in more advanced illness. Caspase-3 immunoreactivity has a tangle-like appearance that coevolves with paired helical filament pathology within neurons. We propose that activation of apoptosis may occur very early in the medial temporal lobe in AD.
Gastard
Myriam C
MC
Division of Neuropathology, Department of Neurology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205-2196, USA.
Troncoso
Juan C
JC
Koliatsos
Vassilis E
VE
D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D008032:Limbic System / Q000201:enzymology* / Q000473:pathology*; D013058:Mass Spectrometry; D016874:Neurofibrillary Tangles / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology; D011233:Precipitin Tests
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases