The DOI matches its Crossref record; 87 of the 88 references it cites were found in a registry or an index.
Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: Evidence for early up-regulation of the endosomal-lysosomal system
Open accessAbstract
In Alzheimer's disease brains, more than 90% of pyramidal neurons in lamina V and 70% in lamina III displayed 2- to 5-fold elevated levels of cathepsin D (Cat D) mRNA by in situ hybridization compared with neurologically normal controls. Most of these cells appeared histologically normal. The less vulnerable nonpyramidal neuron population in lamina IV had relatively normal message levels. Neuronal populations expressing more Cat D mRNA also displayed quantitatively increased Cat D immunoreactive protein. Cat D mRNA expression was only moderately increased in astrocytes. Degenerating neurons exhibited intense immunoreactivity but lowered Cat D mRNA levels. The upregulation of Cat D synthesis and accumulation of hydrolase-laden lysosomes indicate an early activation of the endosomal-lysosomal system in vulnerable neuronal populations, possibly reflecting early regenerative or repair processes. These abnormalities also represent a basis for altered regulation of amyloid precursor protein processing.
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“CTSD gene transcription in neurons is upregulated at early stages of AD (Cataldo et al., 1995) and is accompanied by the accumulation of CTSD forms with decreased activity (P.S.M. and R.A.N., manuscript in preparation).”
From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Cataldo et al., 1995
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“Supporting this hypothesis, the lysosomal system is upregulated in vulnerable cell populations in AD brains [88].”
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Cites
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A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., et al. (2009) · Science · doi:10.1126/science.1174447 · Cited by 2,543
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588
Self-citationMCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 953
Lysosomes as a therapeutic target
Bonam, S. R., Wang, F., & Muller, S. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0036-1 · Cited by 786
Metadata
- Authors
- Cataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., & Nixon, R. A.
- Affiliations
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1995-03
- Volume
- 14
- Issue
- 3
- Pages
- 671-680
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1988022242
- Cited by
- 379
- References
- 88
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 11 · 2022: 5 · 2021: 9 · 2020: 17 · 2019: 18 · 2018: 14 · 2017: 10 · 2016: 18 · 2015: 16 · 2014: 17 · 2013: 12 · 2012: 16
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r35ag010916-08, 5r01ag008278-11)
- National Institute on Aging (AG 08278, AG 10916, P50AG005134, AG 05134)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cathepsin D, Alzheimer's disease, endosomal-lysosomal system, lysosomes, pyramidal neurons, lamina V, lamina III, lamina IV, non-pyramidal neurons, astrocytes, neurodegeneration, APP processing, gene expression
- MeSH terms
- Aged, Alzheimer Disease, Cathepsin D, Humans, Hydrolases, Lysosomes, Middle Aged, Nerve Degeneration, Neurons, Protein Processing, Post-Translational, Endosomes, Reference Values, RNA, Messenger, Blotting, Northern, Gene Expression, Gene Expression Regulation, Enzymologic, Prefrontal Cortex, In Situ Hybridization
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