NACP, a Synaptic Protein Involved in Alzheimer's Disease, Is Differentially Regulated during Megakaryocyte Differentiation

Non-amyloid-β component precursor (NACP) is a presynaptic protein which may play a role in amyloidogenesis in Alzheimer's disease (AD). Since an abnormal function of platelets has been demonstrated in AD, platelets could be used as a model to investigate the role of NACP in this disease. We characterized the patterns of NACP and β-synuclein expression in a megakaryocyte–platelet system (K562). In this hematopoietic cell line, NACP expression was up-regulated during phorbol ester-induced megakaryocytic differentiation, while β-synuclein was down-regulated. Consistent with this, NACP but not β-synuclein was abundantly expressed in platelets. Immunogold electron microscopy of platelets showed that NACP is loosely associated with the plasma membrane, the endomembrane system and, occasionally, with the membrane of secretory α-granules. These findings suggest that coordinate expression of the synuclein family members may play a critical role during hematopoietic cell differentiation. Additionally, expression of the synuclein family members may be developmentally regulated during neural differentiation.