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Keywords:

  • Non-Aβ component of Alzheimer's disease amyloid precursor protein;
  • CNS development;
  • Cytosolic fraction;
  • Particulate fraction;
  • Alzheimer's disease;
  • Parkinson's disease

Abstract

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  2. Abstract

Abstract: The non-Aβ component of Alzheimer's disease amyloid precursor protein (NACP) is predominantly a neuron-specific presynaptic protein that may play a central role in neurodegeneration because NACP fragments are found in Alzheimer's disease amyloid and a mutation in the NACP gene is associated with familial Parkinson's disease. In addition, NACP may play an important role during synaptogenesis and CNS development. To understand better the patterns of NACP expression during development, we analyzed the levels of this protein as well as the levels of another synaptic protein (synaptophysin) by ribonuclease protection assay, western blotting, and immunocytochemistry in fetal, juvenile, and adult mouse brain. From embryonic day 12 to 15, there was a slight increase, which was then followed by a more dramatic increase at later time points. Immunocytochemical staining for NACP increases throughout these stages as well. Although NACP appeared early in CNS development, synaptophysin levels started to rise at a later stage. These findings support the contention that NACP might be important for CNS development. Furthermore, the cytosolic component of NACP precedes the particulate component in development, indicating that a redistribution of the protein to the membrane fraction may be important for events later in neuronal development and in synaptogenesis.

Abbreviations used: E, embryonic day; IR, immunoreactivity; NAC, 35-amino acid, highly amyloidogenic peptide; NACP, non-Aβ component of Alzheimer's disease amyloid precursor protein; P, postnatal day; PNP14, phosphoneuroprotein 14; RPA, ribonuclease protection assay.