Soluble Abeta homeostasis in AD and DS: impairment of anti-amyloidogenic protection by lipoproteins.
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.
Matsubara
Etsuro
E
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
Sekijima
Yoshiki
Y
Tokuda
Takahiko
T
Urakami
Katsuya
K
Amari
Masakuni
M
Shizuka-Ikeda
Masami
M
Tomidokoro
Yasushi
Y
Ikeda
Masaki
M
Kawarabayashi
Takeshi
T
Harigaya
Yasuo
Y
Ikeda
Shu-ichi
S
Murakami
Tetsuro
T
Abe
Koji
K
Otomo
Eiichi
E
Hirai
Shunsaku
S
Frangione
Blas
B
Ghiso
Jorge
J
Shoji
Mikio
M
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
D016229:Amyloid beta-Peptides; D008074:Lipoproteins; D010446:Peptide Fragments