Elsevier

Molecular Brain Research

Volume 33, Issue 1, October 1995, Pages 174-178
Molecular Brain Research

Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease

https://doi.org/10.1016/0169-328X(95)00097-CGet rights and content

Abstract

This study examines the relationship between the levels of apolipoprotein E (apoE) and apolipoprotein J (apoJ, also designated as clusterin) as a function of apoE genotype in the hippocampus and cortex of Alzheimer disease (AD) subjects. These two lipophilic proteins which are involved in the maintenance of lipid homeostasis are both synthesized in the brain by astrocytes. Results indicate a reduction of apoE levels in the hippocampus and frontal cortex that is proportional to the apoE4 allele dose. Conversely, apoJ (clusterin) levels were found to increase proportionately to the number of apoE4 allele dose. These results suggest a compensatory induction of apoJ (clusterin) in the brain of apoE4 AD subjects showing low brain levels of apoE.

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      Nevertheless, these findings suggest that PCSK9 inhibition represents a therapeutic approach for AD therapy. While some studies have shown that apoE levels are upregulated in human AD brains and CSF when compared to controls (Akram et al 2012, Lee et al 2020, Sihlbom et al 2008, Toledo et al 2014), others have reported that apoE levels are not changed (Martinez-Morillo et al 2014, Pirttila et al 1996, Schmidt et al 2014) or decreased (Bertrand et al 1995, Cruchaga et al 2012, Talwar et al 2016). Although studies on apoE mRNA or protein levels in human AD brains have yielded contradictory results, recent studies with single-cell RNA-sequencing, and transcriptomic analyses of isolated microglia have revealed that Apoe is one of the most upregulated genes in a subset of microglia with neurodegenerative phenotype in amyloid mouse models (Keren-Shaul et al 2017, Krasemann et al 2017).

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