Deposition of beta/A4 amyloid in brain is a defining characteristic of
Alzheimer disease (AD); however, the extent to which amyloid deposits
may interfere with normal cellular processes is incompletely understo
od. We examined this issue by means of PC12 cells. After transfection
with DNA coding for 97 amino acids of the beta/A4 C-terminal region of
the amyloid precursor protein, beta/A4 antigen was visible at the cel
l membrane. We report that normal unstimulated PC12 cells exhibit ruff
ling activity at the cell surface when plated on a plastic substrate.
Relative to control cells, however, those that over-expressed the beta
/A4 C-terminal peptide had significantly higher levels of ruffling act
ivity, suggesting a structural and/or functional membrane modification
. Similar cellular alterations, if present, in Alzheimer brain cells,
may indicate disturbances in membrane-associated functions, including
intercellular communication.