Beta-amyloid deposition and neurofibrillary tangle association with caspase activation in Down syndrome.
Individuals with Down syndrome (DS) and Alzheimer's disease (AD) develop senile plaques, neurofibrillary tangles (NFT), and neuron loss. Recent studies demonstrate the activation of apoptotic pathways in AD; less data is available in DS. The DS brain was examined using immunocytochemistry and antibodies against the active fragment of caspase-8 (AC, 8) and to caspase-3 cleavage products of fodrin (CCP), a neuronal cytoskeleton protein. The hippocampus demonstrated widespread accumulation of fodrin CCP and AC8 in NFTs and dystrophic neurites. Individual neurons contained intracellular beta-amyloid (Abeta) and fodrin CCP providing evidence that caspase activation can occur with both NFT and Abeta. Abeta within or around neurons in addition to contributing to NFT formation may also trigger apoptotic pathways. Caspase activation may lead to the cleavage of critical cellular proteins and neuronal cell death associated with DS.
Head
Elizabeth
E
Institute for Brain Aging and Dementia, University of California at Irvine, Irvine, CA 92697-4540, USA. ehead@uci.edu
Lott
I T
IT
Cribbs
David H
DH
Cotman
Carl W
CW
Rohn
Troy T
TT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004314:Down Syndrome / Q000201:enzymology* / Q000473:pathology; D018728:Entorhinal Cortex / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology
D016229:Amyloid beta-Peptides; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases