NDLI: Clinically early-stage CSPα mutation carrier exhibits remarkable terminal stage neuronal pathology with minimal evidence of synaptic loss

Content Provider	Springer Nature : BioMed Central
Author	Benitez, Bruno A. Cairns, Nigel J. Schmidt, Robert E. Morris, John C. Norton, Joanne B. Cruchaga, Carlos Sands, Mark S.
Abstract	Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (AD-ANCL) is a multisystem disease caused by mutations in the DNAJC5 gene. DNAJC5 encodes Cysteine String Protein-alpha (CSPα), a putative synaptic protein. AD-ANCL has been traditionally considered a lysosomal storage disease based on the intracellular accumulation of ceroid material. Here, we report for the first time the pathological findings of a patient in a clinically early stage of disease, which exhibits the typical neuronal intracellular ceroid accumulation and incipient neuroinflammation but no signs of brain atrophy, neurodegeneration or massive synaptic loss. Interestingly, we found minimal or no apparent reductions in CSPα or synaptophysin in the neuropil. In contrast, brain homogenates from terminal AD-ANCL patients exhibit significant reductions in SNARE-complex forming presynaptic protein levels, including a significant reduction in CSPα and SNAP-25. Frozen samples for the biochemical analyses of synaptic proteins were not available for the early stage AD-ANLC patient. These results suggest that the degeneration seen in the patients with AD-ANCL reported here might be a consequence of both the early effects of CSPα mutations at the cellular soma, most likely lysosome function, and subsequent neuronal loss and synaptic dysfunction.
Related Links	https://actaneurocomms.biomedcentral.com/counter/pdf/10.1186/s40478-015-0256-5.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	20515960
DOI	10.1186/s40478-015-0256-5
Journal	Acta Neuropathologica Communications
Issue Number	1
Volume Number	3
Language	English
Publisher	BioMed Central
Publisher Date	2015-11-26
Access Restriction	Open
Subject Keyword	Neurosciences Pathology Neurology Neuronal ceroid lipofuscinosis Cysteine string protein alpha Synaptic loss Neurodegenerative disease Lysosome DNAJC5
Content Type	Text
Resource Type	Case study
Subject	Pathology and Forensic Medicine Neurology (clinical) Cellular and Molecular Neuroscience
Journal Impact Factor	6.2/2023
5-Year Journal Impact Factor	6.8/2023

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