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- Höglund, Kina, 1976, et al.
(författare)
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Cerebrospinal fluid neurogranin in an inducible mouse model of neurodegeneration : A translatable marker of synaptic degeneration
- 2020
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Synapse impairment is thought to be an early event in Alzheimer's disease (AD); dysfunction and loss of synapses are linked to cognitive symptoms that precede neuronal loss and neurodegeneration. Neurogranin (Ng) is a somatodendritic protein that has been shown to be reduced in brain tissue but increased in the cerebrospinal fluid (CSF) of AD patients compared to age-matched controls. High levels of CSF Ng have been shown to reflect a more rapid AD progression. To gauge the translational value of Ng as a biomarker, we developed a new, highly sensitive, digital enzyme-linked immunosorbent assay (ELISA) on the Simoa platform to measure Ng in both mouse and human CSF. We investigated and confirmed that Ng levels are increased in the CSF of patients with AD compared to controls. In addition, we explored how Ng is altered in the brain and CSF of transgenic mice that display progressive neuronal loss and synaptic degeneration following the induction of p25 overexpression. In this model, we found that Ng levels increased in CSF when neurodegeneration was induced, peaking after 2 weeks, while they decreased in brain. Our data suggest that CSF Ng is a biomarker of synaptic degeneration with translational value.
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| 2. |
- Pereira, Joana B., et al.
(författare)
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Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease
- 2020
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. Methods: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. Results: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p =.003) and those who already had PDD (p <.001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p =.004). Baseline and longitudinal Ch4 volumes were associated with cognition (p <.002) and longitudinal Ch4 atrophy predicted future dementia (p =.009). Conclusions: Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.
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