Amyloid-β peptide signature associated with cerebral amyloid angiopathy in familial Alzheimer's disease with APPdup and Down syndrome.

Autor: Kasri A; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France., Camporesi E; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Gkanatsiou E; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Boluda S; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France.; Department of Neuropathology Raymond Escourolle, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France., Brinkmalm G; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Stimmer L; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France., Ge J; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden., Hanrieder J; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK., Villain N; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France., Duyckaerts C; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France.; Department of Neuropathology Raymond Escourolle, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France., Vermeiren Y; Department of Biomedical Sciences, Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.; Division of Human Nutrition and Health, Chair Group Nutritional Biology, Wageningen University and Research (WUR), Wageningen, The Netherlands., Pape SE; Institute of Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, UK., Nicolas G; Department of Genetics, CNRMAJ, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, F-76000, Rouen, France., Laquerrière A; Department of Pathology, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, F-76000, Rouen, France., De Deyn PP; Department of Biomedical Sciences, Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.; Department of Neurology and Alzheimer Center, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands., Wallon D; Department of Neurology, CNRMAJ, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, 76000, Rouen, France., Blennow K; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France.; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute On Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People's Republic of China., Strydom A; Institute of Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, UK., Zetterberg H; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. henrik.zetterberg@gu.se.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. henrik.zetterberg@gu.se.; Department of Neurology and Alzheimer Center, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands. henrik.zetterberg@gu.se.; UK Dementia Research Institute at UCL, London, UK. henrik.zetterberg@gu.se.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China. henrik.zetterberg@gu.se.; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, University of Wisconsin-Madison, Madison, WI, USA. henrik.zetterberg@gu.se., Potier MC; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France. marie-claude.potier@upmc.fr.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2024 Jul 18; Vol. 148 (1), pp. 8. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1007/s00401-024-02756-4
Abstrakt: Alzheimer's disease (AD) is characterized by extracellular amyloid plaques containing amyloid-β (Aβ) peptides, intraneuronal neurofibrillary tangles, extracellular neuropil threads, and dystrophic neurites surrounding plaques composed of hyperphosphorylated tau protein (pTau). Aβ can also deposit in blood vessel walls leading to cerebral amyloid angiopathy (CAA). While amyloid plaques in AD brains are constant, CAA varies among cases. The study focuses on differences observed between rare and poorly studied patient groups with APP duplications (APPdup) and Down syndrome (DS) reported to have higher frequencies of elevated CAA levels in comparison to sporadic AD (sAD), most of APP mutations, and controls. We compared Aβ and tau pathologies in postmortem brain tissues across cases and Aβ peptides using mass spectrometry (MS). We further characterized the spatial distribution of Aβ peptides with MS-brain imaging. While intraparenchymal Aβ deposits were numerous in sAD, DS with AD (DS-AD) and AD with APP mutations, these were less abundant in APPdup. On the contrary, Aβ deposits in the blood vessels were abundant in APPdup and DS-AD while only APPdup cases displayed high Aβ deposits in capillaries. Investigation of Aβ peptide profiles showed a specific increase in Aβx-37, Aβx-38 and Aβx-40 but not Aβx-42 in APPdup cases and to a lower extent in DS-AD cases. Interestingly, N-truncated Aβ2-x peptides were particularly increased in APPdup compared to all other groups. This result was confirmed by MS-imaging of leptomeningeal and parenchymal vessels from an APPdup case, suggesting that CAA is associated with accumulation of shorter Aβ peptides truncated both at N- and C-termini in blood vessels. Altogether, this study identified striking differences in the localization and composition of Aβ deposits between AD cases, particularly APPdup and DS-AD, both carrying three genomic copies of the APP gene. Detection of specific Aβ peptides in CSF or plasma of these patients could improve the diagnosis of CAA and their inclusion in anti-amyloid immunotherapy treatments.
(© 2024. The Author(s).)
Databáze: MEDLINE
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