Accumulation of Alzheimer amyloid-beta peptide in cultured myocytes is enhanced by serum and reduced by cerebrospinal fluid.
Smooth muscle cells cultured from leptomeningeal vessels from old dogs with amyloid-angiopathy accumulate intracellular deposits that are immunoreactive for amyloid-beta peptide (A beta). We used this cellular model in the present study to examine the influence of sera and cerebrospinal fluid on intracellular accumulation of A beta-immunoreactive deposits and on secretion of soluble A beta into culture media. We found that sera from old dogs significantly increased the percentage of A beta-positive smooth muscle cells in culture. The enhanced accumulation of A beta was associated with (a) lower secretion of A beta into media, (b) altered maturation of amyloid-beta-precursor protein (A betaPP) into A betaPP751-770 with faster electrophoretic mobility, (c) increased accumulation of C-terminal fragments of A betaPP (12-15 kD, 10kD and less), and (d) increased secretion of A betaPP into culture media. These findings suggest that age- or disease-related serum factors increase accumulation of A beta by affecting production and processing of A betaPP In contrast, cerebrospinal fluids reduced accumulation of A beta. Involvement of A beta-carrier proteins-apolipoprotein E and transthyretin-in accumulation of A beta is demonstrated. Accumulation of A beta in cultured smooth muscle cells-a model of beta-amyloidosis-may be regulated by factors that alter production and processing of A betaPP as well as the fate of soluble A beta in extracellular space.
Mazur-Kolecka
B
B
New York State Institute for Basic Research in Developmental Disabilities, the Department of Pathological Neurobiology, Staten Island 10314, USA.
Frackowiak
J
J
Carroll
R T
RT
Wisniewski
H M
HM
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000502:physiology*; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D007150:Immunohistochemistry; D009130:Muscle, Smooth / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D001798:Blood Proteins