Clusterin (Apolipoprotein J) Protein Levels Are Increased in Hippocampus and in Frontal Cortex in Alzheimer's Disease

Lidström, Anders; Bogdanović, Nenad; Hesse, Camilla; Volkman, Inga; Davidsson, Pia; Blennow, K.

doi:10.1006/exnr.1998.6892

Cited by 154 publications

(100 citation statements)

References 47 publications

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“…In addition, clusterin has also been widely implicated in human neurodegenerative diseases including Alzheimer's disease (Calero et al 2005), Parkinson's disease (Sasaki et al 2002) and ALS (Grewal et al 1999). Clusterin has been found to be highly expressed in Alzheimer's brain tissue (Lidstrom et al 1998); however, the CSF clusterin levels described in Alzheimer's patients have been inconsistent (Sihlbom et al 2008) or unchanged (Lidstrom et al 2001). The elevation of clusterin expression also has been reported in acute spinal cord injury (Klimaschewski et al 2001).…”

Section: Discussionmentioning

confidence: 99%

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The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Shafie

McLaughlin

Burchmore

et al. 2014

Cell Stress and Chaperones

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Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD.

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Section: Discussionmentioning

confidence: 99%

“…There are several reports of an elevated mRNA clusterin level that correlates with an increase in protein abundance (Lidstrom et al 1998;Grewal et al 1999). Due to a current lack of tissue from IVDD cases, the basis for elevated CSF clusterin in IVDD has not yet been explored.…”

Section: Discussionmentioning

confidence: 99%

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Shafie

McLaughlin

Burchmore

et al. 2014

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…CLU was first implicated in AD back in 1990, when May et al demonstrated expression of the gene in the hippocampus was significantly increased in AD when compared to healthy controls (May et al 1990). CLU protein levels have also been shown to be higher in the frontal cortex and hippocampus of AD patients (Lidstrom et al 1998). Early studies failed to find a link between AD and CLU levels in cerebrospinal fluid (CSF) (Harr et al 1996), however, using newer techniques, it has subsequently been shown that CLU is significantly increased in the CSF of AD patients (Nilselid et al 2006;Sihlbom et al 2008;Thambisetty et al 2012) thereby possibly indicating its utility as a diagnostic biomarker.…”

Section: Clusterin and Admentioning

confidence: 99%

P2‐030: Investigating the Role of Clu, Picalm, and Cr1 in Alzheimer's Disease

Lord

Turton

Braae

et al. 2014

Alzheimer's & Dementia

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In 2009, two large genome wide association studies (GWAS) found associations between common single nucleotide polymorphisms (SNPs) at three loci (CLU, PICALM and CR1) and Alzheimer's disease (AD) risk. The causal variants underlying these associations and how these impact on AD susceptibility remain unclear. Target enrichment and next generation sequencing (NGS) were used to completely resequence the three associated loci in 96 AD patients in an attempt to uncover potentially causative and rare variants that may explain the observed association signals. A pipeline was developed for the handling of pooled NGS data following a comparison of several different combinations of programs. 33 exonic SNPs were found within the three genes, along with over 1000 non-coding variants. To identify the variants most likely to be affecting AD risk, a two pronged approach was adopted. The variants were imputed in a large case-control cohort (2067 cases, 7376 controls) to test for association with AD, and the likely functional consequences of the variants were assessed using in silico resources. Several of the analysed variants showed suggestive or significant association with AD in the imputed data, and/or were predicted to have consequences on the function or regulation of the genes, suggesting avenues for future research in AD genetics. The whole method of pooled, targeted NGS and prioritisation using imputed data for association testing and in silico resources for functional analysis represents a new strategy for tracking down the illusive causation of GWAS signals. PublicationsNext generation sequencing of CLU, PICALM and CR1: pitfalls and potential solutions. Lord J,

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“…There is a correlation between p53 status and secretory clusterin (sCLU) status in various breast cancer cell lines. (4,5), multiple sclerosis (6), atherosclerosis (7,8), and Alzheimer's disease (9)(10)(11). Elevated levels of sCLU protein and mRNA were noted in several different types of human malignancies (12,13), and forced over-expression of sCLU in transformed cell lines resulted in an increased resistance to various chemotherapeutic agents (14).…”

Section: Aimmentioning

confidence: 99%

Investigating the Role of Nuclear Clusterin (nCLU) in Lethality and Genomic Instability in Paclitaxel (Taxol) - Treated Human Breast Cancer Cells

Criswell¹,

Boothman²

2002

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Clusterin (Apolipoprotein J) Protein Levels Are Increased in Hippocampus and in Frontal Cortex in Alzheimer's Disease

Cited by 154 publications

References 47 publications

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

P2‐030: Investigating the Role of Clu, Picalm, and Cr1 in Alzheimer's Disease

Investigating the Role of Nuclear Clusterin (nCLU) in Lethality and Genomic Instability in Paclitaxel (Taxol) - Treated Human Breast Cancer Cells

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