Universität zu Köln

Barrera-Ocampo, Alvaro ORCID: 0000-0003-0906-9293, Arlt, Soenke, Matschke, Jakob ORCID: 0000-0001-6080-0198, Hartmann, Ursula, Puig, Berta, Ferrer, Isidre, Zuerbig, Petra, Glatzel, Markus ORCID: 0000-0002-7720-8817, Sepulveda-Falla, Diego ORCID: 0000-0003-0176-2042 and Jahn, Holger ORCID: 0000-0003-3607-7651 (2016). Amyloid-beta Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease. J. Neuropathol. Exp. Neurol., 75 (9). S. 903 - 917. CARY: OXFORD UNIV PRESS INC. ISSN 1554-6578

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Abstract

The mechanisms leading to amyloid-beta (A beta) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with A beta plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant A beta precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced A beta 40 and A beta 42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor A beta accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of A beta species.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Barrera-Ocampo, Alvaro UNSPECIFIED orcid.org/0000-0003-0906-9293 UNSPECIFIED Arlt, Soenke UNSPECIFIED UNSPECIFIED UNSPECIFIED Matschke, Jakob UNSPECIFIED orcid.org/0000-0001-6080-0198 UNSPECIFIED Hartmann, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Puig, Berta UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferrer, Isidre UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuerbig, Petra UNSPECIFIED UNSPECIFIED UNSPECIFIED Glatzel, Markus UNSPECIFIED orcid.org/0000-0002-7720-8817 UNSPECIFIED Sepulveda-Falla, Diego UNSPECIFIED orcid.org/0000-0003-0176-2042 UNSPECIFIED Jahn, Holger UNSPECIFIED orcid.org/0000-0003-3607-7651 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-264013
DOI:	10.1093/jnen/nlw065
Journal or Publication Title:	J. Neuropathol. Exp. Neurol.
Volume:	75
Number:	9
Page Range:	S. 903 - 917
Date:	2016
Publisher:	OXFORD UNIV PRESS INC
Place of Publication:	CARY
ISSN:	1554-6578
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INSULIN-DEGRADING ENZYME; SULFATE PROTEOGLYCAN; EXTRACELLULAR-MATRIX; MESSENGER-RNA; CATHEPSIN-L; IN-VIVO; EXPRESSION; GLYCOSAMINOGLYCANS; DEGRADATION; BIOMARKERS Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26401