Cited by 379Alzheimer's disease research and treatmentsProtease and Inhibitor MechanismsDementia and Cognitive Impairment Research

Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: Evidence for early up-regulation of the endosomal-lysosomal system

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Cataldo, Anne M, Barnett, Jody L, Berman, Stephen A, Li, Jinhe, Quarless, Shelley, Bursztajn, Sherry, Lippa, Carol, Nixon, Ralph A·1995·Neuron

Abstract

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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Crossref · 10.1016/0896-6273(95)90324-0

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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
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
  • Health Sciences › Medicine › Physiology › 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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