Amyloidosis causes downregulation of SorLA, SorCS1 and SorCS3 expression in mice

TY - JOUR

T1 - Amyloidosis causes downregulation of SorLA, SorCS1 and SorCS3 expression in mice

AU - Hermey, Guido

AU - Hoffmeister-Ullerich, Sabine A

AU - Merz, Barbara

AU - Groß, Dagmar

AU - Kuhl, Dietmar

AU - Kins, Stefan

PY - 2019/8/27

Y1 - 2019/8/27

N2 - Accumulation of β-amyloid peptide (Aβ) is regarded as a primary cause of Alzheimer's disease (AD). Aβ is derived by sequential cleavage of the amyloid precursor protein (APP). Alterations in the subcellular targeting of APP are thought to affect the degree of Aβ production. Sorting receptors, such as SorLA, convey subcellular targeting of APP. Dysfunction of SorLA, and likely of the related receptors SorCS1 and SorCS3, cause AD. Nevertheless, disease progression could also provoke altered expression of the receptors. Here, we assessed if Aβ plaque formation promotes altered expression of SorLA, SorCS1 and SorCS3. We analyzed transcript levels during aging and after amyloidosis in brain areas characterized by early amyloid plaque formation in an AD mouse model (APPPS1) and wild types. We observed stable expression levels during aging (1-12 months). After plaque formation, SorCS1 and SorLA expression were markedly reduced in the frontal cerebral cortex and to a minor extent in the hippocampus, whereas SorCS3 expression was solely reduced in the frontal cerebral cortex. Our results indicate that disease progression, associated with Aβ accumulation, can negatively regulate expression of the receptors.

AB - Accumulation of β-amyloid peptide (Aβ) is regarded as a primary cause of Alzheimer's disease (AD). Aβ is derived by sequential cleavage of the amyloid precursor protein (APP). Alterations in the subcellular targeting of APP are thought to affect the degree of Aβ production. Sorting receptors, such as SorLA, convey subcellular targeting of APP. Dysfunction of SorLA, and likely of the related receptors SorCS1 and SorCS3, cause AD. Nevertheless, disease progression could also provoke altered expression of the receptors. Here, we assessed if Aβ plaque formation promotes altered expression of SorLA, SorCS1 and SorCS3. We analyzed transcript levels during aging and after amyloidosis in brain areas characterized by early amyloid plaque formation in an AD mouse model (APPPS1) and wild types. We observed stable expression levels during aging (1-12 months). After plaque formation, SorCS1 and SorLA expression were markedly reduced in the frontal cerebral cortex and to a minor extent in the hippocampus, whereas SorCS3 expression was solely reduced in the frontal cerebral cortex. Our results indicate that disease progression, associated with Aβ accumulation, can negatively regulate expression of the receptors.

U2 - 10.1515/hsz-2019-0146

DO - 10.1515/hsz-2019-0146

M3 - SCORING: Journal article

C2 - 31095505

VL - 400

SP - 1181

EP - 1189

JO - BIOL CHEM

JF - BIOL CHEM

SN - 1431-6730

IS - 9

ER -