Immunolocalization of an Amino-Terminal Fragment of Apolipoprotein E in the Pick's Disease Brain

Abstract

Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer's disease (AD) has been well described, the role that apoE plays in other neurodegenerative diseases, including Pick's disease, is not well established. To examine a possible role of apoE in Pick's disease, an immunohistochemical analysis was performed utilizing a novel site-directed antibody that is specific for an amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE cleavage fragment (nApoECF) antibody, consistently labeled Pick bodies within area CA1 of the hippocampus in 4 of the 5 cases examined. Co-localization of the nApoECF antibody with PHF-1, a general marker for Pick bodies, as well as with an antibody to caspase-cleaved tau (TauC3) was evident within the hippocampus. While staining of the nApoECF antibody was robust in area CA1, little co-localization with PHF-1 in Pick bodies within the dentate gyrus was observed. A quantitative analysis indicated that approximately 86% of the Pick bodies identified in area CA1 labeled with the nApoECF antibody. The presence of truncated apoE within Pick bodies suggests a broader role of apoE beyond AD and raises the question as to whether this protein contributes to pathogenesis associated with Pick's disease.

Level of PICALM, a key component of clathrin-mediated endocytosis, is correlated with levels of phosphotau and autophagy-related proteins and is associated with tau inclusions in AD, PSP and Pick disease

“…APOE4 is aberrantly cleaved and its cleaved fragments interact with tau in AD brains (Huang et al, 2001;Rohn et al, 2012). APOE immunoreactivity is also found in tau positive inclusions of other tau-related neurodegenerative disorders such as Pick disease (Farrer et al, 1995;Hayashi et al, 1998;Rohn et al, 2013). PICALM and APOE risk alleles are associated with brain atrophy and cognitive function in LOAD patients (Morgen et al, 2014).…”

Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease

“…Responsible is calpain-mediated digestion, a broadly expressed calciumdependent protease Zoltewicz et al, 2012). There is also evidence for caspase-3 and caspase-9 GFAP cleavage products (Acarin et al, 2007;Rohn et al, 2002Rohn et al, , 2013bMouser et al, 2006). In addition, the cystein protease caspase 6 cleaves GFAP at Asp 225 resulting in two proteolytic fragments of 24 kDa and 26 kDa (Chen et al, 2013).…”

Association of high-density lipoprotein and apolipoprotein E genetic variants with age-related macular degeneration

“…ApoE plays a role in the metabolism of TG-rich lipoproteins (chylomicrons and very LDL) as well as in the association of this metabolism with HDL (3,30) . Importantly, apoE3 and particularly apoE4 reveal affinity with the membrane receptor apoB/E, whereas apoE2 is does not, which influences serum levels of TC, LDLc, and TG (19) .…”