TY - JOUR
T1 - A dynamic relationship between intracellular and extracellular pools of Aβ
AU - Oddo, Salvatore
AU - Caccamo, Antonella
AU - Smith, Ian F.
AU - Green, Kim N.
AU - LaFerla, Frank M.
N1 - Funding Information:
Supported by the National Institute on Aging (AG0212982 to F.M.L.) and the Alzheimer's Association (IIRG-02-3767 to F.M.L.).
PY - 2006/1
Y1 - 2006/1
N2 - The accumulation of the amyloid-β peptide (Aβ) in the brain is considered to have a primary role in Alzheimer's disease (AD). In addition to the extracellular accumulation of Aβ in the parenchyma and cerebrovasculature, emerging evidence indicates that intraneuronal Aβ also plays a pathophysiological role in AD. It is unclear, however, if the intracellular and extracellular pools of Aβ are unrelated or connected. In these studies, we sought to establish a relationship between these two pools of Aβ. We identified an inverse relationship between intracellular and extracellular Aβ in the 3xTg-AD transgenic model of AD. Using an immunotherapy approach, we further found that extracellular Aβ was cleared before intracellular Aβ. After the antibody dissipated, however, the reappearance of extracellular plaques was preceded by the accumulation of iatraneuronal Aβ. Taken together, these results provide strong experimental evidence that intraneuronal Aβ may serve as a source for some of the extracellular amyloid deposits.
AB - The accumulation of the amyloid-β peptide (Aβ) in the brain is considered to have a primary role in Alzheimer's disease (AD). In addition to the extracellular accumulation of Aβ in the parenchyma and cerebrovasculature, emerging evidence indicates that intraneuronal Aβ also plays a pathophysiological role in AD. It is unclear, however, if the intracellular and extracellular pools of Aβ are unrelated or connected. In these studies, we sought to establish a relationship between these two pools of Aβ. We identified an inverse relationship between intracellular and extracellular Aβ in the 3xTg-AD transgenic model of AD. Using an immunotherapy approach, we further found that extracellular Aβ was cleared before intracellular Aβ. After the antibody dissipated, however, the reappearance of extracellular plaques was preceded by the accumulation of iatraneuronal Aβ. Taken together, these results provide strong experimental evidence that intraneuronal Aβ may serve as a source for some of the extracellular amyloid deposits.
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U2 - 10.2353/ajpath.2006.050593
DO - 10.2353/ajpath.2006.050593
M3 - Article
C2 - 16400022
AN - SCOPUS:30344448543
SN - 0002-9440
VL - 168
SP - 184
EP - 194
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -