Apolipoprotein D mRNA expression is elevated in PDAPP transgenic mice

Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Journal of Neurochemistry (Impact Factor: 4.28). 01/2002; 79(5):1059-64. DOI: 10.0000/096381898336501
Source: PubMed


Apolipoprotein D (apoD) expression is known to be elevated in select regions of rodent and human brain in association with different types of CNS pathology. To investigate a potential role for apoD in the neuropathology of Alzheimer's disease, we have measured apoD mRNA expression in transgenic mice expressing mutated human amyloid precursor protein under control of platelet-derived growth factor promoter (PDAPP mice). In situ hybridization analysis revealed increased apoD mRNA expression in brains of aged (26 months) PDAPP transgenic mice compared to aged littermate controls. These increases were most prominent in the hippocampal fimbria, corpus callosum and other white matter tracts. No substantial increases in expression were observed in white matter regions in young (6 months) PDAPP transgenic mice compared to young controls. Comparison between aged and young control mice revealed increased apoD expression in similar white matter regions of the aged animals. These findings suggest that, although increases in apoD expression are a normal feature of brain aging, super-increases may represent a glial cell compensatory response to beta-amyloid deposition in Alzheimer's disease.

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Available from: Elizabeth A Thomas, Nov 22, 2014
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    • "Specifically, ApoD has been demonstrated to be significantly upregulated in the brain of a transgenic mouse with an overexpressed highly amyloidogenic, that is, Aβ producing, form of human amyloid precursor protein. As is typical for AD, this effect was observed only in aged (26-month-old), but not young (6-month-old) animals (Thomas et al., 2001c). While these results do not necessarily imply a neuroprotective role for ApoD in AD, recent biochemical data do in fact suggest precisely such a role. "
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    ABSTRACT: Apolipoprotein D (ApoD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that ApoD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of ApoD to arachidonic acid and its derivatives, which play a central role in healthy brain function. ApoD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that ApoD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, ApoD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of ApoD because of its antioxidant and anti-inflammatory activity. ApoD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging.
    Neurobiology of aging 02/2014; 35(7). DOI:10.1016/j.neurobiolaging.2014.01.148 · 5.01 Impact Factor
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    • "ApoD is known to be induced in the brain not only during virus infections (Prosniak et al., 2001; Johnston et al., 2001) but also during several neuropathological conditions such as schizophrenia (Thomas et al., 2001a), Alzheimer's disease, (Thomas et al., 2001b) etc. It is considered to be an acute phase protein involved in the removal of lipids during nerve cell degeneration and provision of lipids during the regenerative phase (Reindl et al., 2001). "
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    ABSTRACT: This study identified nine genes whose expression is upregulated in the central nervous system (CNS) of mice during Japanese encephalitis virus (JEV) infection. These include: cathepsin S, oligoadenylate synthetase (OAS), GARG49/IRG2, lymphocyte antigen-6A (Ly-6A), macrophage activation gene-2 (Mpa2), early growth response gene1 (Egr1), pyrimidine 5'-nucleotidase (P5N), apolipoprotein D (ApoD) and STAT1. Activation of all nine genes during JEV infection was confirmed by Northern blot analysis. JEV replication was inhibited in the majority of mice immunized with Biken JEV vaccine, and these mice also exhibited reduced expression of JEV-inducible CNS genes. Thus, there is a good correlation between virus load and upregulation of host CNS genes. It was also demonstrated that all the CNS genes activated by JEV are also upregulated during rabies virus infection. In addition, GARG49, STAT1, cathepsin S and ApoD are known to be upregulated in the CNS by Sindbis virus, an alphavirus, and this supports the proposal that common host cell pathways are activated in the CNS by different neurotropic viruses.
    Journal of General Virology 08/2003; 84(Pt 7):1729-35. DOI:10.1099/vir.0.18826-0 · 3.18 Impact Factor
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    • "It has been previously associated with AD; however, its role is unclear. Increased apoD mRNA and/or protein expression has been detected in the cerebrospinal fluid (CSF), hippocampus, and selected cortical cell populations of AD subjects (Belloir et al 2001; Kalman et al 2000; Terrisse et al 1998) and in the brains of an Alzheimer's transgenic mouse model (PDAPP transgenic mice; these mice over-express the human amyloid precursor protein under the control of the platelet-derived growth factor promoter) (Thomas et al 2001b); however, unlike other apolipoproteins, such as apoE, apoA-1, apoJ, and apoB, the cortical senile plaques and neurofibrillary tangles observed in AD are immunonegative for apoD (Belloir et al 2001; Calero et al 2000; Harr et al 1996; Kalman et al 2000; Namba et al 1991). We have previously demonstrated that apoD protein expression is elevated in prefrontal cortex and other select regions from subjects with schizophrenia and bipolar disorder, and we have suggested that elevated apoD levels may be useful as a marker for pathology associated with psychiatric disorders (Thomas et al 2001a, 2003). "
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    ABSTRACT: Apolipoprotein E (apoE) has been implicated in the pathology of AD ever since inheritance of the epsilon4 allele was shown to be an important risk factor for the development of AD. Apolipoprotein D (apoD) is elevated in association with several central nervous system disorders, including Alzheimer's disease (AD), and has been proposed to be an especially robust marker for brain regions specifically affected by particular neuropathologies. Progressive cognitive decline is the core clinical feature of AD and is associated with disturbances in the prefrontal cortex. We measured apoD levels in prefrontal cortex samples obtained postmortem from 20 autopsy-confirmed AD subjects and 40 control subjects. Enzyme-linked immunosorbent assay analysis revealed a significant increase in apoD expression in AD subjects compared with control subjects (.218+/-.029 microg/mg protein vs.117+/-.011 microg/mg protein; p=0003). There was no significant difference in apoD expression between early-onset and late-onset Alzheimer's subjects. Apolipoprotein D expression levels were not correlated with apoE levels, nor were they correlated with inheritance of the APOE epsilon4 allele. These findings suggest that apoD may be related to the cognitive decline observed in AD patients and that apoD and apoE likely play different roles in the pathogenesis of AD.
    Biological Psychiatry 08/2003; 54(2):136-41. · 10.26 Impact Factor
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