Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice

Abstract

Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaque load, as assessed by immunohistochemical staining. Conversely, transgenic expression of neuronal apoD reduced hippocampal plaque load by approximately 35%. This latter finding was associated with a 60% decrease in amyloid β 1-40 peptide levels, and a 34% decrease in insoluble amyloid β 1-42 peptide. Assessment of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point toward a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD. Disciplines Medicine and Health Sciences Publication DetailsLi, H., Ruberu, K., Sanz Munoz, S., Jenner, A. M., Spiro, A., Zhao, H., Rassart, E., Sanchez, D., Ganfornina, M. peptide levels, and a 34% decrease in insoluble amyloid-beta 1-42 peptide. Assessment of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point towards a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD.

Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex

“…This transcriptional regulation agrees with a number of widely known correlational studies showing high expression levels of ApoD in many aged model organisms, as well as in humans and rodents suffering from neurodegenerative conditions (reviewed by Dassati et al, 2014;Rassart et al, 2000). In this context, a recent report links ApoD expression levels to the regulation of amyloid plaque pathology in a mouse model of AD (Li et al, 2015).…”

Myelin extracellular leaflet compaction requires apolipoprotein D membrane management to optimize lysosomal‐dependent recycling and glycocalyx removal

“…We have previously analyzed ApoD expression in the nervous system under stress, damage or pathological conditions (Bajo‐Grañeras et al, ; Ganfornina et al, ; Ganfornina et al, ; Garcia‐Mateo et al, ; Li et al, ; Sanchez et al, ), and found that it is up‐regulated in glial cells in both CNS and PNS (reviewed by Dassati, Waldner, & Schweigreiter, ). In the healthy brain, the major cell type expressing ApoD is the mature oligodendrocyte (Supporting Information, Figure S1a and Ganfornina et al, ; Navarro, Del Valle, & Tolivia, ; Ong et al, ; Provost et al, ; Soreq et al, ), and the oligodendrocyte‐specific transcriptome is particularly altered in ApoD‐KO mice (Bajo‐Grañeras et al, ).…”

Low sulfated heparins target multiple proteins for central nervous system repair

“…In contrast, DCM contained factors that were related to chemokine signaling and Candidates that are secreted and of interest in these cultures are highlighted in bold and reflect those indicated in Figure 7b 4.4 | Factors found in CCM A2M, a broad spectrum proteinase inhibitor and a carrier of growth factors was increased in CCM. It has been associated with neurological disorders (multiple sclerosis [MS] and AD), other inflammatory diseases of the CNS and nerve injury (Li et al, 2015;Reindl et al, 2001). Apolipoprotein D (ApoD) is a secreted glycoprotein with many roles within lipid transport, detected in neurons, astrocytes, and oligodendrocytes (Ong et al, 1999).…”

“…Apolipoprotein D (ApoD) is a secreted glycoprotein with many roles within lipid transport, detected in neurons, astrocytes, and oligodendrocytes (Ong et al, 1999). It has been associated with neurological disorders (multiple sclerosis [MS] and AD), other inflammatory diseases of the CNS and nerve injury (Li et al, 2015;Reindl et al, 2001). Interestingly levels were not above threshold in MC-Demy, suggesting a nerve damage component to its upregulated expression.…”