Ultrastructural localization of intraneuronal Abeta-peptide in Alzheimer disease brains

Autopsied brain tissue from Alzheimer's disease patients and old non-demented controls was studied after immunocytochemistry with the 4G8 monoclonal antibody that recognizes amyloid-beta peptides. Intraneuronal 4G8-positive reaction product was detected in all of the studied brains. The same brain regions in the Alzheimer's disease samples consistently showed both more immunopositive neurons and more stained reaction product per neuron than those from the non-demented brains. Ultrastructurally, the immunopositive reaction product accumulated in clusters of cytoplasmic elements that had a lipofuscin-like appearance, showed a fibrogranular content and were also closely apposed to lipid droplets located either on their periphery or within them. The most strongly 4G8-immunopositive elements had diffuse limits with their fibrogranular content free in the cytoplasm, whereas elements either without or showing only light immunoreaction had a limiting membrane. All immunopositive neurons displayed a similar pattern of clumping heterochromatin. The hypothetical neurotoxic role of intraneuronal amyloid-beta peptides free in the cytoplasm is discussed as is the possible relationship between the amyloid-beta peptides recognized by the 4G8 antibody and the lipid droplets which would presumably contain esterified cholesterol.