Impaired synaptic function is linked to cognition in Parkinson's disease

Selnes, Per; Stav, Ane Løvli; Johansen, Krisztina K.; Bjørnerud, Atle; Coello, Christopher; Auning, Eirik; Kalheim, Lisa Flem; Almdahl, Ina Selseth; Hessen, Erik; Zetterberg, Henrik; Blennow, Kaj; Aarsland, Dag; Fladby, Tormod

doi:10.1002/acn3.446

Cited by 23 publications

(26 citation statements)

References 46 publications

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“…Furthermore, increased Ng has been linked to cognitive decline and conversion from MCI to AD . In this study focusing on parkinsonian disorders, confirming some studies but contradicting others, we find decreased levels of Ng in PD compared to controls. We also found decreased levels of Ng in MSA and PSP using both assays and in PDD using Ng‐EI.…”

Section: Discussionsupporting

confidence: 85%

“…Contradicting one study, but supporting another, we found no association between levels of Ng and motor dysfunction . Furthermore, supporting results from one study, we found no associations between Ng and cognitive impairment in parkinsonian disorders.…”

Section: Discussionsupporting

confidence: 76%

“…In AD, high CSF Ng has been interpreted to reflect synaptic (dendritic) degeneration whereas reduction of Ng in PD has been suggested to be a result of reduced synaptic activity, possibly attributable to presynaptic α‐syn deposits …”

Section: Discussionmentioning

confidence: 99%

“…Few studies have examined CSF Ng in PD, finding unchanged or decreased levels of Ng compared to controls . Even scarcer are studies on Ng and cognitive decline or motor dysfunction, and results are conflicting .…”

mentioning

confidence: 99%

“…12 Few studies have examined CSF Ng in PD, finding unchanged or decreased levels of Ng compared to controls. 5,9,13 Even scarcer are studies on Ng and cognitive decline or motor dysfunction, and results are conflicting. 9,13,14 In PSP, MSA, corticobasal syndrome (CBS), and DLB/PDD, Ng has been found to be unchanged compared to controls and lower compared to AD.…”

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confidence: 99%

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Cerebrospinal Fluid Levels of Neurogranin in Parkinsonian Disorders

et al. 2019

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Background CSF concentration of neurogranin has been suggested as a biomarker for synapse dysfunction. Objectives To investigate CSF neurogranin in parkinsonian disorders compared to controls and Alzheimer's disease and the possible correlations between neurogranin and cognitive and motor impairment. Methods We included 157 patients with PD, 29 with PD with dementia, 11 with dementia with Lewy bodies, 26 with MSA, 21 with PSP, 6 with corticobasal syndrome, 47 controls, and 124 with Alzheimer's disease. CSF neurogranin was measured using two enzyme‐linked immunosorbent assays; from EUROIMMUN and the University of Gothenburg. Results We found a strong correlation between CSF neurogranin‐EI and CSF neurogranin–University of Gothenburg (Rs = 0.890; P < 0.001). Neurogranin was decreased in PD, PD with dementia, MSA, and PSP compared to controls and Alzheimer's disease. Neurogranin did not correlate with motor or cognitive impairment, longitudinal decline, or progression to dementia in PD. Conclusions CSF neurogranin is decreased in parkinsonian disorders compared to controls, emphasizing the importance of synaptic dysfunction in these disorders. © 2019 International Parkinson and Movement Disorder Society

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Cerebrospinal Fluid Levels of Neurogranin in Parkinsonian Disorders

et al. 2019

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α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

et al. 2018

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Background: The objective of this study was to investigate the discriminating value of a range of CSF α‐synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls. Methods: We applied our recently published enzyme‐linked immunosorbent assays to measure the CSF levels of total α‐synuclein, oligomeric α‐synuclein, and phosphorylated α‐synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α‐synuclein levels between groups. We used backward‐elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α‐synuclein species and Alzheimer's disease biomarkers. Results: CSF levels of total α‐synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls ( P < 0.001). In contrast, CSF levels of oligomeric α‐synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease ( P < 0.05) and controls ( P < 0.001). No group differences were found for phosphorylated α‐synuclein. In dementia with Lewy bodies and PD, CSF total α‐synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid‐β 1‐42 . The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid‐β 1‐42 , tau, total α‐synuclein, oligomeric α‐synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α‐synuclein resulted in an AUC of 0.83. CSF α‐synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD. Conclusions: CSF α‐synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α‐synuclein and total α‐synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Neurogranin-like immunoreactivity in the zebrafish brain during development

et al. 2022

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Neurogranin (Nrgn) is a neural protein that is enriched in the cerebral cortex and is involved in synaptic plasticity via its interaction with calmodulin. Recently we reported its expression in the brain of the adult zebrafish (Alba-González et al. J Comp Neurol 530:1569–1587, 2022). In this study we analyze the development of Nrgn-like immunoreactivity (Nrgn-like-ir) in the brain and sensory structures of zebrafish embryos and larvae, using whole mounts and sections. First Nrgn-like positive neurons appeared by 2 day post-fertilization (dpf) in restricted areas of the brain, mostly in the pallium, epiphysis and hindbrain. Nrgn-like populations increased noticeably by 3 dpf, reaching an adult-like pattern in 6 dpf. Most Nrgn-like positive neurons were observed in the olfactory organ, retina (most ganglion cells, some amacrine and bipolar cells), pallium, lateral hypothalamus, thalamus, optic tectum, torus semicircularis, octavolateralis area, and viscerosensory column. Immunoreactivity was also observed in axonal tracts originating in Nrgn-like neuronal populations, namely, the projection of Nrgn-like immunopositive primary olfactory fibers to olfactory glomeruli, that of Nrgn-like positive pallial cells to the hypothalamus, the Nrgn-like-ir optic nerve to the pretectum and optic tectum, the Nrgn-like immunolabeled lateral hypothalamus to the contralateral region via the horizontal commissure, the octavolateralis area to the midbrain via the lateral lemniscus, and the viscerosensory column to the dorsal isthmus via the secondary gustatory tract. The late expression of Nrgn in zebrafish neurons is probably related to functional maturation of higher brain centers, as reported in the mammalian telencephalon. The analysis of Nrgn expression in the zebrafish brain suggests that it may be a useful marker for specific neuronal circuitries.

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Impaired synaptic function is linked to cognition in Parkinson's disease

Cited by 23 publications

References 46 publications

Cerebrospinal Fluid Levels of Neurogranin in Parkinsonian Disorders

Cerebrospinal Fluid Levels of Neurogranin in Parkinsonian Disorders

α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

Neurogranin-like immunoreactivity in the zebrafish brain during development

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