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 β-protein (Aβ) deposits in the cerebral cortices of patients with Alzheimer's disease (AD) were investigated immunohistochemically to determine their carboxy terminal sequences. Antibodies specific for Aβ terminating at residue valine₄₀ (Aβ40) and at residues alanine₄₂/threonine₄₃ (Aβ42) were used. Virtually all parenchymal Aβ deposits were positive for Aβ42. Many of these deposits were also partially or completely labeled for Aβ40. The degree of Aβ40 labeling varied from area to area within a given brain and from AD case to AD case. In contrast to parenchymal deposits, Aβ40 labeled essentially all the vascular deposits which constitute amyloid angiopathy (AA), with Aβ42 occurring variably in some of these deposits. Occasional AA was found, however, in which Aβ42 predominated or was exclusively deposited. Such a diversity of Aβ species, both in brain parenchyma and in AA, suggests that multiple C-terminal processing mechanisms occur in the cell types responsible for these deposits.