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Lysosomal cathepsin D is upregulated in Alzheimer's disease neocortex and may be a marker for neurofibrillary degeneration.
Chai, Yuek Ling; Chong, Joyce R; Weng, Jiaju; Howlett, David; Halsey, Andrea; Lee, Jasinda H; Attems, Johannes; Aarsland, Dag; Francis, Paul T; Chen, Christopher P; Lai, Mitchell K P.
Afiliación
  • Chai YL; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Chong JR; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Weng J; Memory Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore.
  • Howlett D; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Halsey A; Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
  • Lee JH; Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
  • Attems J; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Aarsland D; Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
  • Francis PT; Department NVS, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institute, Huddinge, Sweden.
  • Chen CP; Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
  • Lai MKP; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
Brain Pathol ; 29(1): 63-74, 2019 01.
Article en En | MEDLINE | ID: mdl-30051532
Alzheimer's disease (AD) is characterized by accumulation of ß-amyloid plaques (AP) and neurofibrillary tangles (NFT) in the cortex, together with synaptic loss and amyloid angiopathy. Perturbations in the brain lysosomal system, including the cathepsin family of proteases, have been implicated in AD where they may be involved in proteolytic clearance of misfolded and abnormally aggregated peptides. However, the status of cathepsin D (catD) is unclear in Lewy body dementia, the second most common form of neurodegenerative dementia after AD, and characterized by Lewy bodies (LB) containing aggregated α-synuclein. Furthermore, earlier reports of catD changes in AD have not been entirely consistent. We measured CatD immunoreactivities in the temporal (Brodmann area BA21) and parietal (BA40) cortices of well characterized AD brains as well as two clinical subtypes of Lewy body dementia, namely Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB), known to show varying degrees of concomitant AD pathology. Increased catD immunoreactivities in AD were found for both neocortical regions measured, where they also correlated with neuropathological NFT scores and phosphorylated pSer396 tau burden, and appeared to co-localize at least partly to NFT-containing neurons. In contrast, catD was increased only in BA40 in DLB and not at all in PDD, did not correlate with LB scores, and did not appreciably co-localize with α-synuclein inclusions. Our study suggests that catD upregulation may be an adaptive response to AD-related processes leading to neurofibrillary degeneration, but may not be directly associated with formation of α-synuclein inclusions in Lewy body dementia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Catepsina D / Neocórtex / Enfermedad de Alzheimer Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Brain Pathol Asunto de la revista: CEREBRO / PATOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Catepsina D / Neocórtex / Enfermedad de Alzheimer Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Brain Pathol Asunto de la revista: CEREBRO / PATOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Suiza