TY - JOUR
T1 - Brain interstitial oligomeric amyloid β increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease
AU - Takeda, Shuko
AU - Hashimoto, Tadafumi
AU - Roe, Allyson D
AU - Hori, Yukiko
AU - Spires-Jones, Tara L
AU - Hyman, Bradley T
PY - 2013/8
Y1 - 2013/8
N2 - There is a growing body of evidence that soluble oligomeric forms of amyloid β (Aβ) play a critical role in Alzheimer's disease (AD). Despite the importance of soluble Aβ oligomers as a therapeutic target for AD, the dynamic metabolism of these Aβ species in vivo has not been elucidated because of the difficulty in monitoring brain Aβ oligomers in living animals. Here, using a unique large pore-sized membrane microdialysis, we characterized soluble Aβ oligomers in brain interstitial fluid (ISF) of awake, freely moving APP/PS1 transgenic and control WT mice. We could detect high-molecular-weight (HMW) and low-molecular-weight (LMW) Aβ oligomers in the brain ISF of living animals, which increased dramatically in an age-dependent manner (5- to 8-fold increase, 4 vs. 17-18 mo). Notably, HMW Aβ decreased more slowly than other forms of Aβ after acute γ-secretase inhibition [% decrease from the baseline (HMW vs. LMW) was 36.9 vs. 74.1% (Aβ40, P
AB - There is a growing body of evidence that soluble oligomeric forms of amyloid β (Aβ) play a critical role in Alzheimer's disease (AD). Despite the importance of soluble Aβ oligomers as a therapeutic target for AD, the dynamic metabolism of these Aβ species in vivo has not been elucidated because of the difficulty in monitoring brain Aβ oligomers in living animals. Here, using a unique large pore-sized membrane microdialysis, we characterized soluble Aβ oligomers in brain interstitial fluid (ISF) of awake, freely moving APP/PS1 transgenic and control WT mice. We could detect high-molecular-weight (HMW) and low-molecular-weight (LMW) Aβ oligomers in the brain ISF of living animals, which increased dramatically in an age-dependent manner (5- to 8-fold increase, 4 vs. 17-18 mo). Notably, HMW Aβ decreased more slowly than other forms of Aβ after acute γ-secretase inhibition [% decrease from the baseline (HMW vs. LMW) was 36.9 vs. 74.1% (Aβ40, P
U2 - 10.1096/fj.13-229666
DO - 10.1096/fj.13-229666
M3 - Article
C2 - 23640054
VL - 27
SP - 3239
EP - 3248
JO - The FASEB Journal
JF - The FASEB Journal
SN - 0892-6638
IS - 8
ER -