Human NCL Neuropathology
Open accessAbstract
The neuronal ceroid lipofuscinoses (NCL) currently encompass fourteen genetically different forms, CLN1 to CLN14, but are all morphologically marked by loss of nerve cells, particularly in the cerebral and cerebellar cortices, and the cerebral and extracerebral formation of lipopigments. These lipopigments show distinct ultrastructural patterns, i.e., granular, curvilinear/rectilinear and fingerprint profiles. They contain-although to a different degree among the different CLN forms-subunit C of ATP synthase, saposins A and D, and beta-amyloid proteins. Extracerebral pathology, apart from lipopigment formation, which provides diagnostic information, is scant or non-existent. The retina undergoes atrophy in all childhood forms. While many new data and findings have been obtained by immunohistochemistry in mouse and other animal models, similar findings in human NCL are largely missing, thus recommending respective studies of archived brain tissues. The newly described NCL forms, i.e., CLN 10 to CLN 14, also require further studies to provide complete neuropathology. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)".
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Lipofuscin is a key pathology in neuronal ceroid lipofuscinosis and GRN-linked frontotemporal dementia.
“While lipofuscin is key pathology in neuronal ceroid lipofuscinosis and GRN-linked frontotemporal dementia”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [69]
The Light microscopy section calls lipopigment formation a hallmark of neuronal ceroid lipofuscinosis. The GRN entry in Table 3 concerns a form of NCL; neither it nor the passages found for “frontotemporal dementia” establish lipofuscin as a key pathology in GRN-linked frontotemporal dementia. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn C. elegans, granulins accumulate with age.
“In C. elegans, granulins accumulate with age, and multi-granulin fragments accumulate in diseased brain regions from patients with GRN-FTD and AD.133”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [133]
The Electron microscopy section discusses accumulation of NCL-associated proteins, and Table 3 mentions GRN-associated pathology, but neither addresses granulin accumulation in C. elegans. Searches for C. elegans, age-related granulin accumulation, and multi-granulin fragments found no passage supporting the cited sentence. Page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIndividual granulins seemingly inhibit CTSD activity.
“In contrast, individual granulins seemingly inhibit CTSD activity.133”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [133]
The Light microscopy section discusses cathepsin D deficiency in CLN10, while Table 3 lists CTSD and GRN separately in NCL pathology. Neither passage addresses whether individual granulins inhibit CTSD activity. Searches for that interaction and for progranulin-related enzyme inhibition found no supporting passage in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measuredMulti-granulin fragments accumulate in diseased brain regions from patients with GRN-FTD and AD.
“In C. elegans, granulins accumulate with age, and multi-granulin fragments accumulate in diseased brain regions from patients with GRN-FTD and AD.133”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [133]
The Electron microscopy section discusses accumulation of NCL-associated proteins, while Table 3 lists GRN-associated lipopigments in sweat gland cells. Neither addresses multi-granulin fragments in GRN-FTD or AD brain regions; searches for those fragments and diseases found no supporting passage in our copy. The passages do not specify page numbers. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 4
- L. Åberg, T. Autti, J.D. Cooper, M. Elleder, M. Haltia, A. Jalanko, C. Kitzmüller, O. Kopra, S.E. Mole, A. Nuutila, L. Peltonen, M.L. Punkari, J. Rapola, J. Tyynelä, CLN5 (chapter 9), in: S.E. Mole, R.E. Williams, H.H. Goebel (Eds.), The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd ed.Oxford University Press, Oxford/UK 2011, pp. 140-158.
- M. Chang, J.D. Cooper, B.L. Davidson, O.P. van Diggelen, M. Elleder, H.H. Goebel, A.A. Golabek, E. Kida, A. Kohlschütter, P. Lobel, S.E. Mole, A. Schulz, D.E. Sleat, M.J. Warburton, K.E. Wisniewski, CLN2 (chapter 7), in: S.E. Mole, R.E. Williams, H.H. Goebel (Eds.), The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd ed.Oxford University Press, Oxford, UK 2011, pp. 80-109.
- G. Anderson, M. Elleder, H.H. Goebel, S. Carpenter, M. Haltia, B.D. Lake, J. Rapola, Morphological diagnostic and pathological considerations (chapter 4), in: S.E. Mole, R.E. Williams, H.H. Goebel (Eds.), The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd ed.Oxford University Press, Oxford/UK 2011, pp. 35-49.
- S.E. Mole, R.E. Williams, H.H. Goebel (Eds.), The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd ed.Oxford University Press, Oxford, UK, 2011.
Cited by
Sorted by citations
Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91 · see citing works
Pathomechanisms in the neuronal ceroid lipofuscinoses
Nelvagal, H. R., Lange, J., Takahashi, K., Tarczyluk-Wells, M. A., & Cooper, J. D. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.165570 · Cited by 80 · see citing works
Lane-Donovan, C., Paredes, M., & Kao, A. W. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102854 · Cited by 3 · see citing works
- Authors
- Radke, J., Stenzel, W., & Goebel, H. H.
- Affiliations
- Stiftung Charité (DE)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Goebel, Hans H.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 1852
- Issue
- 10
- Pages
- 2262-2266
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W272134036
- Cited by
- 122
- References
- 0
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 15 · 2023: 10 · 2022: 13 · 2021: 16 · 2020: 9 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 5 · 2014: 1
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 366 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Petra Matylewski and Silvia Stefaniak
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- neuronal ceroid lipofuscinosis, Batten disease, neuropathology, lipopigments, saposins, amyloid-beta, retinal atrophy, cerebral cortex, cerebellum, immunohistochemistry, mouse model
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
