Elsevier

Neuroscience

Volume 113, Issue 2, 12 August 2002, Pages 301-310
Neuroscience

Seladin-1 transcription is linked to neuronal degeneration in Alzheimer’s disease

https://doi.org/10.1016/S0306-4522(02)00180-XGet rights and content

Abstract

Seladin-1 is a gene recently shown to be down-regulated in brain regions selectively degenerated in Alzheimer’s disease. The sequence of seladin-1 shares similarities with flavin-adenine-dinucleotide-dependent oxidoreductases and it has been found to protect cells from apoptotic cell death. In this work, we show that the transcription of seladin-1 is selectively down-regulated in the brain areas affected in Alzheimer’s disease. The down-regulation in seladin-1 transcription was associated with hyperphosphorylated tau seen as linkage to immunohistochemically detected paired helical filament tau, neuritic plaques and neurofibrillary tangles. In contrast, no association was found between seladin-1 transcription and β-amyloid deposition when analyzing human samples or tissue from transgenic animals. Furthermore, the relative transcription of seladin-1 was found to fluctuate during aging in the transgenic mouse model of Alzheimer’s disease. The fluctuation was enhanced by Alzheimer’s disease causing mutations in presenilin-1 and amyloid precursor protein genes. Finally, seladin-1 transcription was found to be up-regulated in mouse N2a cells induced to undergo apoptosis with okadaic acid.

The results presented here indicate that seladin-1 transcription is selectively down-regulated in brain regions vulnerable to Alzheimer’s disease and this down-regulation is associated with the hyperphosphorylation of tau protein.

Section snippets

Human post-mortem material

Post-mortem samples (Kuopio Brain Bank) obtained since 1991 were evaluated. This study is part of the project focusing on risk genes of AD that has been approved by the local ethical committee, and the use of tissue by the Office of Legal Health Care Affairs. The patients had been clinically assessed by neurologists and the diagnosis of AD was based on the NINCDS-ADRDA (McKhann et al., 1984) and diagnosis of other dementias on the DSM-III-R criteria (American Psychiatric Association, 1987) (

Seladin-1 transcription in human brain tissue

Differential transcription of seladin-1 in temporal and occipital cortical post-mortem brain samples of demented and non-demented subjects was studied using the semi-quantitative RT-PCR method (Fig. 1A). The relative transcription of seladin-1 in human temporal cortex was highly correlated with the transcription in occipital cortex (R=0.767; P<0.001). Thus, to detect averaged differences between these two cortices, we used the ratio of seladin-1 transcription in temporal versus occipital cortex

Discussion

We studied the relative transcription of seladin-1 in temporal and occipital cortices in demented and non-demented subjects using a semi-quantitative RT-PCR method. We found a decrease in the transcription of seladin-1 in temporal cortex when compared to occipital cortex in AD. The seladin-1 transcription was linked with the hallmark lesions of AD, NPs and NFTs whereas no linkage was found between seladin-1 transcription and Aβ. In addition, we investigated the changes in seladin-1

Acknowledgements

The authors thank Marjo Heikkinen, Petra Mäkinen, Tarja Kauppinen, Heikki Luukkonen and Hannu Tiainen for their excellent technical help. The study was supported by the Health Research Council of the Academy of Finland, EVO Grants (5142, 5152 and 5510) of Kuopio University Hospital and the EU 5th Framework Programme (QLK6-CT-1999-02112).

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