Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease.

Autor:	Li X; Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven (University of Leuven), Leuven, Belgium.; Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium., Tsolis KC; Laboratory of Molecular Bacteriology, Rega Institute, Department of Microbiology and Immunology, KU Leuven (University of Leuven), Leuven, Belgium., Koper MJ; Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven (University of Leuven), Leuven, Belgium.; Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.; Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, KU Leuven (University of Leuven), Leuven, Belgium.; Center for Brain and Disease Research, VIB, Leuven, Belgium., Ronisz A; Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven (University of Leuven), Leuven, Belgium.; Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium., Ospitalieri S; Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven (University of Leuven), Leuven, Belgium.; Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium., von Arnim CAF; Department of Neurology, University of Ulm, Ulm, Germany.; Department of Geriatrics, University Medical Center Göttingen, Göttingen, Germany., Vandenberghe R; Department of Neurology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium.; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven (University of Leuven), Leuven, Belgium., Tousseyn T; Department of Pathology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium., Scheuerle A; Institute of Pathology, University of Ulm, Ulm, Germany., Economou A; Laboratory of Molecular Bacteriology, Rega Institute, Department of Microbiology and Immunology, KU Leuven (University of Leuven), Leuven, Belgium., Carpentier S; BIOMED facility for SYstems BIOlogy based MAss spectrometry, KU Leuven (University of Leuven), Leuven, Belgium., Otto M; Department of Neurology, University of Ulm, Ulm, Germany., Thal DR; Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven (University of Leuven), Leuven, Belgium.; Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.; Department of Pathology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2021 Jun; Vol. 17 (6), pp. 946-958. Date of Electronic Publication: 2021 Apr 19.
DOI:	10.1002/alz.12345
Abstrakt:	Proteome profile changes in Alzheimer's disease (AD) brains have been reported. However, it is unclear whether they represent a continuous process, or whether there is a sequential involvement of distinct proteins. To address this question, we used mass spectrometry. We analyzed soluble, dispersible, sodium dodecyl sulfate, and formic acid fractions of neocortex homogenates (mainly Brodmann area 17-19) from 18 pathologically diagnosed preclinical AD, 17 symptomatic AD, and 18 cases without signs of neurodegeneration. By doing so, we identified four groups of AD-related proteins being changed in levels in preclinical and symptomatic AD cases: early-responding, late-responding, gradually-changing, and fraction-shifting proteins. Gene ontology analysis of these proteins and all known AD-risk/causative genes identified vesicle endocytosis and the secretory pathway-related processes as an early-involved AD component. In conclusion, our findings suggest that subtle changes involving the secretory pathway and endocytosis precede severe proteome changes in symptomatic AD as part of the preclinical phase of AD. The respective early-responding proteins may also contribute to synaptic vesicle cycle alterations in symptomatic AD. (© 2021 the Alzheimer's Association.)
Databáze:	MEDLINE
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