Abundance of the longer Aβ₄₂ in neocortical and cerebrovascular amyloid β deposits in Swedish familial Alzheimer's disease and Down's syndrome

Recent studies have demonstrated the deposition of amyloid β (Aβ) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to Aβ peptides, we examined the immunocytochemical distribution of Aβ₄₀ and Aβ₄₂ species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid β precursor protein (AβPP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal Aβ deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. Aβ₄₂ was evident in almost all parenchymal deposits as well as many vascular deposits. Although Aβ₄₀ was present in meningeal and intraparenchymal vessels, deposits containing this shorter peptide reactivity were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable abundance of Aβ₄₂ in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published AβPP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble Aβ production and Aβ₄₂ species to be predominant, it would appear that the double AβPP mutations in Swedish FAD largely result in the deposition of the longer Aβ₄₂ in vivo.