G protein subunit levels in fibroblasts from familial Alzheimer's disease patients: lower levels of the high molecular weight Gs α isoform in patients with decreased β-adrenergic receptor stimulated cAMP formation

Abstract

Abnormalities in G protein linked signal transduction pathways have been detected in fibroblasts from individuals with familial and sporadic Alzheimer's disease. The present study used Gs α, Gi α, Gq α and Go α G protein subunit antisera, immunoblotting and densitometry to quantify levels of these proteins in control fibroblasts and in fibroblasts from individuals with familial Alzheimer's disease (FAD). The FAD fibroblasts were from individuals with the APP K670N,M671L mutation, different presenilin 1 (PS1) mutations and one fibroblast cell line from an individual with FAD of unknown genetic aetiology. Results revealed a significant reduction in the large Gs α subunit in fibroblasts with the PS1 mutations and in the fibroblast cell line of unknown genetic aetiology, when compared to control levels. This decrease was not apparent in the APP K670N,M671L FAD fibroblasts. Immunoreactivity for Go α was not detected in any of the fibroblast cell lines. No differences were observed in Gi α or Gq α levels when comparing any of the control and Alzheimer's disease fibroblast groups. We conclude that with the exception of decreased levels of the large Gs α subunit, gross alterations in the levels of the Gi α, Gq α and Go α are not associated with the G protein-coupled signal transduction disturbances described previously for some of these FAD fibroblasts.