title: Soluble Abeta homeostasis in AD and DS: impairment of anti-amyloidogenic protection by lipoproteins.
abstract: In order to assess whether lipoproteins are physiologically able to balance and modulate the sAbeta homeostasis in vivo, soluble Abeta levels in lipoprotein-depleted plasma were measured as a function of age in normal controls, Alzheimer's disease (AD) patients, and Down's syndrome (DS) cases. The reshaping of sAbeta homeostasis, in particular the sAbeta42-lipoprotein interaction, takes place over normal-60's, whereas mild AD patients appear to have impaired this anti-amyloidogenic mechanism resulting in a significant increase of lipoprotein-free sAbeta42. Similar loss of function takes place in Down's syndrome patients. Lipoprotein-free sAbeta remains significantly elevated from the pre-symptomatic through the symptomatic stages of the disease, and declines with the progression of the AD-like pathology. The dissociation of sAbeta from lipoprotein-particles also occurs in brain parenchyma and the presence of soluble dimeric lipoprotein-free Abeta prior to its parenchymal deposition in AD brains would support the hypothesis that functionally declined lipoproteins may be major determinants in the production of metabolic conditions leading to higher levels of sAbeta species and cerebral amyloidosis.
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Schikata-cho, Okayama, Okayama 700-8558, Japan. meturo@cc.okayama-u.ac.jp
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sekijima
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.forename: Katsuya
authors.initials: K
authors.lastname: Urakami
authors.forename: Masakuni
authors.initials: M
authors.lastname: Amari
authors.forename: Masami
authors.initials: M
authors.lastname: Shizuka-Ikeda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomidokoro
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Harigaya
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Eiichi
authors.initials: E
authors.lastname: Otomo
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Hirai
authors.forename: Blas
authors.initials: B
authors.lastname: Frangione
authors.forename: Jorge
authors.initials: J
authors.lastname: Ghiso
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000145:classification / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000378:metabolism / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000378:metabolism; D016555:Matched-Pair Analysis; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D012016:Reference Values; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides; D008074:Lipoproteins; D010446:Peptide Fragments