Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis

Mattsson, Niklas; Axelsson, Markus; Haghighi, Sara; Malmeström, Clas; Wu, Guoxin; Anckarsäter, Rolf; Sankaranarayanan, Sethu; Andréasson, Ulf; Fredrikson, Sten; Gundersen, Astrid S; Johnsen, Lisbeth; Fladby, Tormod; Tarkowski, Andrej; Trysberg, Estelle; Wallin, Anders; Anckarsäter, Henrik; Lycke, Jan; Andersen, Oluf; Simon, Adam J.; Blennow, Kaj; Zetterberg, Henrik

doi:10.1177/1352458508100031

Cited by 58 publications

(52 citation statements)

References 34 publications

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“…In fact, CSF Ab42 is the earliest nongenetic biomarker we know of in AD. Low CSF Ab42 concentrations in the absence of senile plaques have been reported in neuroinflammatory conditions, for example, bacterial meningitis [63], multiple sclerosis [64], human immunodeficiency virus (HIV)-associated dementia [65], and Lyme neuroborreliosis [66], and are often accompanied by biomarker evidence of a general reduction in APP metabolites, for example, secreted forms of APP, which is not typical of AD [50]. Besides Ab42, several other Ab isoforms are present in CSF.…”

Section: Csf Ab42mentioning

confidence: 96%

CSF in Alzheimer's Disease

Zetterberg

Lautner

Skillbäck

et al. 2014

Advances in Clinical Chemistry

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Section: Csf Ab42mentioning

confidence: 96%

CSF in Alzheimer's Disease

Zetterberg

Lautner

Skillbäck

et al. 2014

Advances in Clinical Chemistry

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“…Interestingly, cerebrospinal fluid (CSF) from MS patients exhibits decreased BACE1 activity, suggesting decreased β2 cleavage and consequent alterations in normal VGSC α expression and localization. Low BACE1 activity in MS is linked to worsened disease severity and longer disease duration, and BACE1 expression continues to decrease throughout disease progression (132). …”

Section: Channelopathies and Pathophysiology Of Vgsc β Subunitsmentioning

confidence: 99%

Sodium Channel β Subunits: Emerging Targets in Channelopathies

O’Malley

Isom

2015

Annu. Rev. Physiol.

218

255

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Voltage-gated sodium channels (VGSCs) are responsible for initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Originally called “auxiliary,” we now know that β subunit proteins are multifunctional signaling molecules that play roles in both excitable and non-excitable cell types, and with or without the pore-forming α subunit present. β subunits function in VGSC and potassium channel modulation, cell adhesion, and gene regulation, with particularly important roles in brain development. Mutations in the genes encoding β subunits are linked to a number of diseases, including epilepsy, sudden death syndromes like SUDEP and SIDS, and cardiac arrhythmia. While VGSC β subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target.

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“…APP is cleaved by an integral membrane aspartyl protease ( β -site APP-cleaving enzyme 1, BACE1), which results in the release of N-terminal β -cleaved soluble APP ( β -sAPP). The C-terminal fragment is further processed by γ -secretase to yield the amyloid beta (A β 42) and the APP intracellular domain [122]. APP can also undergo α -secretase-mediated cleavage, which results in the release of the solubile α -sAPP [123].…”

Section: Biomarkers Of Neuroaxonal Damage In Multiple Sclerosismentioning

confidence: 99%

Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

Dujmović

2011

Multiple Sclerosis International

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Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS) are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested.

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Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis

Abstract: These results suggest an involvement of BACE1 in the MS disease process.

Cited by 58 publications

References 34 publications

CSF in Alzheimer's Disease

CSF in Alzheimer's Disease

Sodium Channel β Subunits: Emerging Targets in Channelopathies

Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

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