Abstract
Sortilin 1 (SORL1) is a transmembrane sorting receptor that regulates the intracellular trafficking of β-amyloid precursor protein (βAPP). Interactions between SORL1 and βAPP result in the decreased processing of βAPP into toxic amyloid-β42 (Aβ42) peptides that accumulate in Alzheimer's disease brain. Here, we report selectively decreased levels of SORL1 in limbic and occipital regions of Alzheimer brain that inversely correlate with amyloid plaque and neurofibrillary tangle density. Reduced SORL1, coupled to elevated β-amyloid cleaving enzyme, presenilin-1 and increased Aβ42 peptide secretion, was observed after incubation of cultured human neural cells with the proinflammatory cytokine interleukin-1β. The results suggest that SORL1 deficits may not only promote the pathogenic processing of βAPP but may also contribute to Aβ42-mediated inflammatory signaling in stressed human brain cells.
| Original language | English |
|---|---|
| Pages (from-to) | 1187-1191 |
| Number of pages | 5 |
| Journal | NeuroReport |
| Volume | 18 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jul 1 2007 |
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Keywords
- β-amyloid precursor protein processing
- Alzheimer's disease
- Amyloid-β42 peptides
- Brain gene expression
- Cholesterol
- Inflammatory signaling
- Lipoprotein receptors
- SORL1/LR11
- Sortilin
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Reduction of sortilin-1 in Alzheimer hippocampus and in cytokine-stressed human brain cells. / Zhao, Yuhai; Cui, Jian Guo; Lukiw, Walter J.
In: NeuroReport, Vol. 18, No. 11, 01.07.2007, p. 1187-1191.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduction of sortilin-1 in Alzheimer hippocampus and in cytokine-stressed human brain cells
AU - Zhao, Yuhai
AU - Cui, Jian Guo
AU - Lukiw, Walter J.
PY - 2007/7/1
Y1 - 2007/7/1
N2 - Sortilin 1 (SORL1) is a transmembrane sorting receptor that regulates the intracellular trafficking of β-amyloid precursor protein (βAPP). Interactions between SORL1 and βAPP result in the decreased processing of βAPP into toxic amyloid-β42 (Aβ42) peptides that accumulate in Alzheimer's disease brain. Here, we report selectively decreased levels of SORL1 in limbic and occipital regions of Alzheimer brain that inversely correlate with amyloid plaque and neurofibrillary tangle density. Reduced SORL1, coupled to elevated β-amyloid cleaving enzyme, presenilin-1 and increased Aβ42 peptide secretion, was observed after incubation of cultured human neural cells with the proinflammatory cytokine interleukin-1β. The results suggest that SORL1 deficits may not only promote the pathogenic processing of βAPP but may also contribute to Aβ42-mediated inflammatory signaling in stressed human brain cells.
AB - Sortilin 1 (SORL1) is a transmembrane sorting receptor that regulates the intracellular trafficking of β-amyloid precursor protein (βAPP). Interactions between SORL1 and βAPP result in the decreased processing of βAPP into toxic amyloid-β42 (Aβ42) peptides that accumulate in Alzheimer's disease brain. Here, we report selectively decreased levels of SORL1 in limbic and occipital regions of Alzheimer brain that inversely correlate with amyloid plaque and neurofibrillary tangle density. Reduced SORL1, coupled to elevated β-amyloid cleaving enzyme, presenilin-1 and increased Aβ42 peptide secretion, was observed after incubation of cultured human neural cells with the proinflammatory cytokine interleukin-1β. The results suggest that SORL1 deficits may not only promote the pathogenic processing of βAPP but may also contribute to Aβ42-mediated inflammatory signaling in stressed human brain cells.
KW - β-amyloid precursor protein processing
KW - Alzheimer's disease
KW - Amyloid-β42 peptides
KW - Brain gene expression
KW - Cholesterol
KW - Inflammatory signaling
KW - Lipoprotein receptors
KW - SORL1/LR11
KW - Sortilin
UR - http://www.scopus.com/inward/record.url?scp=34250876949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250876949&partnerID=8YFLogxK
U2 - 10.1097/WNR.0b013e32821c56c4
DO - 10.1097/WNR.0b013e32821c56c4
M3 - Article
C2 - 17589324
AN - SCOPUS:34250876949
VL - 18
SP - 1187
EP - 1191
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 11
ER -