The DOI matches its Crossref record.
Elevated Levels of the Endosomal‐Lysosomal Proteinase Cathepsin D in Cerebrospinal Fluid in Alzheimer Disease
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
Cites
Still being checked.
Cited by
Sorted by citations
Items 101–107 of 107
Odagiri, S., Mori, F., Tanji, K., Kuroda, N., & Wakabayashi, K. (2013) · Institutional Repositories DataBase (IRDB)
Wang, Y. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3bg2hr4j
Marshall, K. E., Mengham, K., Spink, M. C., Vania, L., Pollard, H. J., Darrow, M. C., Duke, E., Harkiolaki, M., & Serpell, L. C. (2022) · Research Square · doi:10.21203/rs.3.rs-2189678/v1
Caruso, M. G., Dohm-Hansen, S., Donoso, F., Williams, Z. A. P., Grabrucker, S., Lavelle, A., English, J. A., Nicolas, S., O’Leary, O. F., & Nolan, Y. M. (2026) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2026.07.001
Mechanisms of autophagy–lysosome pathway impairment in Alzheimer's disease
Lü, K., Lu, Y., Tang, R., Dong, X., Zhuang, P., Gao, Y., Cheng, M., Wang, Y., & Wang, Y. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261460879
Longitudinal dynamics of gene expression and metabolomics in an aging population cohort
Moustafa, J. S. E.-S., Ramisch, A., Raza, Y. N., Leday, G. G. R., Jiao, Y., Wang, D., Stevens, M., Roberts, A. L., Tomlinson, M., Yan, X., et al. (2026) · Science · doi:10.1126/science.aed6452
Rellevància del TNF i l’esfingomielinasa àcida en la fibrogènesi hepàtica
Tarrats, N. (2012) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
