Accumulation of Alzheimer amyloid-β peptide in cultured myocytes is enhanced by serum and reduced by cerebrospinal fluid

Abstract

Smooth muscle cells cultured from leptomeningeal vessels from old dogs with amyloid-angiopathy accumulate intracellular deposits that are immunoreactive for amyloid-β peptide (Aβ). We used this cellular model in the present study to examine the influence of sera and cerebrospinal fluid on intracellular accumulation of Aβ-immunoreactive deposits and on secretion of soluble Aβ into culture media. We found that sera from old dogs significantly increased the percentage of Aβ-positive smooth muscle cells in culture. The enhanced accumulation of Aβ was associated with (a) lower secretion of Aβ into media, (b) altered maturation of amyloid-β-precursor protein (AβPP) into AΠP751-770 with faster electrophoretic mobility, (c) increased accumulation of C-terminal fragments of AβPP (12-15 kD, 10kD and less), and (d) increased secretion of AβPP into culture media. These findings suggest that age- or disease-related serum factors increase accumulation of Aβ by affecting production and processing of AβPP. In contrast, cerebrospinal fluids reduced accumulation of Aβ. Involvement of Aβ-carrier proteins-apolipoprotein E and transthyretin-in accumulation of Aβ is demonstrated. Accumulation of Aβ in cultured smooth muscle cells-a model of β-amyloidosis-may be regulated by factors that alter production and processing of AβPP as well as the fate of soluble Aβ in extracellular space.