Beta-amyloid deposition and neurofibrillary tangle association with caspase activation in Down syndrome

Neurosci Lett. 2002 Sep 13;330(1):99-103. doi: 10.1016/s0304-3940(02)00705-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Down Syndrome / enzymology*
  • Down Syndrome / pathology
  • Entorhinal Cortex / chemistry
  • Entorhinal Cortex / enzymology
  • Entorhinal Cortex / pathology
  • Enzyme Activation / physiology
  • Humans
  • Middle Aged
  • Neurofibrillary Tangles / chemistry
  • Neurofibrillary Tangles / enzymology*
  • Neurofibrillary Tangles / pathology


  • Amyloid beta-Peptides
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases