title: Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta deposits in Swedish familial Alzheimer's disease and Down's syndrome.
abstract: Recent studies have demonstrated the deposition of amyloid beta (A beta) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to A beta peptides, we examined the immunocytochemical distribution of A beta 40 and A beta 42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid beta precursor protein (A beta PP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal A beta deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. A beta 42 was evident in almost all parenchymal deposits as well as many vascular deposits. Although A beta 40 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 A beta 42 in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published A beta PP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble A beta production and A beta 40 species to be predominant, it would appear that the double A beta PP mutations in Swedish FAD largely result in the deposition of the longer A beta 42 in vivo.
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: D L
authors.initials: DL
authors.lastname: Cohen
authors.forename: B D
authors.initials: BD
authors.lastname: Greenberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Savage
authors.forename: N E
authors.initials: NE
authors.lastname: Bogdanovic
authors.forename: B
authors.initials: B
authors.lastname: Winblad
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
authors.forename: A
authors.initials: A
authors.lastname: Adem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D002540:Cerebral Cortex / Q000737:chemistry*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D010507:Periodicity; D013548:Sweden
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins