Variable Deposition of Amyloid β-Protein (Aβ) with the Carboxy-Terminus that Ends at Residue Valine40 (Aβ40) in the Cerebral Cortex of Patients with Alzheimer's Disease: A Double-Labeling Immunohistochemical Study with Antibodies Specific for Aβ40 and the Aβ that Ends at Residues Alanine42/Threonine43 (Aβ42)

Abstract

Amyloid beta-protein (A beta) deposits in the cerebral cortices of patients with Alzheimer's disease (AD) were investigated immunohistochemically to determine their carboxy terminal sequences. Antibodies specific for A beta terminating at residue valine40 (A beta 40) and at residues alanine42/threonine43 (A beta 42) were used. Virtually all parenchymal A beta deposits were positive for A beta 42. Many of these deposits were also partially or completely labeled for A beta 40. The degree of A beta 40 labeling varied from area to area within a given brain and from AD case to AD case. In contrast to parenchymal deposits, A beta 40 labeled essentially all the vascular deposits which constitute amyloid angiopathy (AA), with A beta 42 occurring variably in some of these deposits. Occasional AA was found, however, in which A beta 42 predominated or was exclusively deposited. Such a diversity of A beta species, both in brain parenchyma and in AA, suggests that multiple C-terminal processing mechanisms occur in the cell types responsible for these deposits.