Abstract
In order to assess whether lipoproteins are physiologically able to balance and modulate the sAβ homeostasis in vivo, soluble Aβ 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 sAβ homeostasis, in particular the sAβ42-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 sAβ42. Similar loss of function takes place in Down's syndrome patients. Lipoprotein-free sAβ 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 sAβ from lipoprotein-particles also occurs in brain parenchyma and the presence of soluble dimeric lipoprotein-free Aβ 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 sAβ species and cerebral amyloidosis.
| Original language | English |
|---|---|
| Pages (from-to) | 833-841 |
| Number of pages | 9 |
| Journal | Neurobiology of Aging |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Aug 2004 |
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Keywords
- Aβ dimer
- Alzheimer's disease
- Down's syndrome
- Lipoprotein-free Aβ
- sAβ homeostasis
ASJC Scopus subject areas
- Clinical Neurology
- Biological Psychiatry
- Developmental Neuroscience
- Neurology
- Psychology(all)
Cite this
Soluble Aβ homeostasis in AD and DS : Impairment of anti-amyloidogenic protection by lipoproteins. / Matsubara, Etsuro; Sekijima, Yoshiki; Tokuda, Takahiko; Urakami, Katsuya; Amari, Masakuni; Shizuka-Ikeda, Masami; Tomidokoro, Yasushi; Ikeda, Masaki; Kawarabayashi, Takeshi; Harigaya, Yasuo; Ikeda, Shu Ichi; Murakami, Tetsuro; Abe, Koji; Otomo, Eiichi; Hirai, Shunsaku; Frangione, Blas; Ghiso, Jorge; Shoji, Mikio.
In: Neurobiology of Aging, Vol. 25, No. 7, 08.2004, p. 833-841.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Soluble Aβ homeostasis in AD and DS
T2 - Impairment of anti-amyloidogenic protection by lipoproteins
AU - Matsubara, Etsuro
AU - Sekijima, Yoshiki
AU - Tokuda, Takahiko
AU - Urakami, Katsuya
AU - Amari, Masakuni
AU - Shizuka-Ikeda, Masami
AU - Tomidokoro, Yasushi
AU - Ikeda, Masaki
AU - Kawarabayashi, Takeshi
AU - Harigaya, Yasuo
AU - Ikeda, Shu Ichi
AU - Murakami, Tetsuro
AU - Abe, Koji
AU - Otomo, Eiichi
AU - Hirai, Shunsaku
AU - Frangione, Blas
AU - Ghiso, Jorge
AU - Shoji, Mikio
PY - 2004/8
Y1 - 2004/8
N2 - In order to assess whether lipoproteins are physiologically able to balance and modulate the sAβ homeostasis in vivo, soluble Aβ 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 sAβ homeostasis, in particular the sAβ42-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 sAβ42. Similar loss of function takes place in Down's syndrome patients. Lipoprotein-free sAβ 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 sAβ from lipoprotein-particles also occurs in brain parenchyma and the presence of soluble dimeric lipoprotein-free Aβ 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 sAβ species and cerebral amyloidosis.
AB - In order to assess whether lipoproteins are physiologically able to balance and modulate the sAβ homeostasis in vivo, soluble Aβ 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 sAβ homeostasis, in particular the sAβ42-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 sAβ42. Similar loss of function takes place in Down's syndrome patients. Lipoprotein-free sAβ 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 sAβ from lipoprotein-particles also occurs in brain parenchyma and the presence of soluble dimeric lipoprotein-free Aβ 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 sAβ species and cerebral amyloidosis.
KW - Aβ dimer
KW - Alzheimer's disease
KW - Down's syndrome
KW - Lipoprotein-free Aβ
KW - sAβ homeostasis
UR - http://www.scopus.com/inward/record.url?scp=4544307730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4544307730&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2003.10.004
DO - 10.1016/j.neurobiolaging.2003.10.004
M3 - Article
C2 - 15212837
AN - SCOPUS:4544307730
VL - 25
SP - 833
EP - 841
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 7
ER -