Cited by 107Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCerebrospinal fluid and hydrocephalus

Elevated Levels of the Endosomal‐Lysosomal Proteinase Cathepsin D in Cerebrospinal Fluid in Alzheimer Disease

Schwagerl, A. L., Mohan, P. S., Cataldo, A. M., Vonsattel, J. P., Kowall, N. W., Nixon, R. A.·1995·Journal of Neurochemistry

Abstract

Lysosomal hydrolases are normally intracellular enzymes but are abundant extracellularly within senile plaques in Alzheimer disease and in other conditions where beta-amyloid accumulates. To examine whether acid hydrolases released from abnormal hydrolase-laden neurons are detectable in CSF, we measured levels of the major aspartic proteinase of lysosomes, cathepsin D (Cat D), in ventricular CSF collected after death from 30 patients with Alzheimer disease, 14 patients with Huntington disease, and seven patients with other neurodegenerative diseases. The levels of Cat D-immunoreactive protein, expressed as micrograms per milliliter of protein, determined by western blot immunoassay using a polyclonal antiserum against human brain Cat D, were more than fourfold higher in the Alzheimer patients than in the other patient groups (p < 0.0005). Cat D activity, assayed separately against [14C]methemoglobin at pH 3.2, was also significantly elevated but less than Cat D content. The lower specific activity of Cat D in Alzheimer CSF therefore indicated that the abnormally accumulated Cat D included a high proportion of inactive enzyme. These results indicate that abnormal Cat D release from affected neurons into the extracellular space is an active, ongoing process in Alzheimer brain. In addition, the levels of this enzyme and possibly other lysosomal hydrolases in CSF may prove to be useful biological markers of Alzheimer disease.

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Crossref · 10.1046/j.1471-4159.1995.64010443.x

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  • Ventricular CSF obtained postmortem from AD patients has substantially elevated levels of CTSD with markedly lowered specific activity compared with CSF from individuals with Huntington's disease or from non-neurologic disease controls.

    “we previously reported that ventricular CSF obtained postmortem from AD patients has substantially elevated levels of CTSD with markedly lowered specific activity compared with CSF from individuals with Huntington's disease or from non-neurologic disease controls (Schwagerl et al., 1995).”

    From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Schwagerl et al., 1995

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Authors
Schwagerl, A. L., Mohan, P. S., Cataldo, A. M., Vonsattel, J. P., Kowall, N. W., & Nixon, R. A.
Affiliations
  • Georgetown University (US)
  • McLean Hospital (US)
  • Harvard University (US)
  • United States Department of Veterans Affairs (US)
Corresponding author
Nixon, R. A.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
1995-01
Volume
64
Issue
1
Pages
443-446
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1974250737
Cited by
107
References
0
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 7 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 4 · 2012: 3
FWCI
3.32
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r35ag010916-08, 5r01mh031862-24)
  • National Institute on Aging (AG 10916)
  • National Institute of Mental Health (MH31862)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
cathepsin D, Alzheimer's disease, cerebrospinal fluid, lysosomal enzymes, aspartic protease, amyloid plaques, amyloid-beta, Huntington's disease, neurodegenerative diseases, enzyme activity, biomarkers
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Cathepsins, Female, Humans, Huntington Disease, Lysosomes, Male, Middle Aged, Endosomes, Blotting, Western

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