The distribution of amyloid beta precursor protein in canine brain

Okuda, Ryutaro; Uchida, Katsuhisa; Tateyama, Shingo; Yamaguchi, R.; Nakayama, H.; Goto, Naoto

doi:10.1007/s004010050071

Cited by 3 publications

(3 citation statements)

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“…Furthermore, it is conceivable that differences in proteolytic processing and/or secretion of APLP2 between cell types may lead to differential accumulation of the precursor isoforms and its derivatives. Immunocytochemical methods have been used to study the distribution of APP in CNS (Card et al, 1988;Shivers et al, 1988;Kawarabayashi et al, 1991;Martin et al, 1991;Imaizumi et al, 1993;Okuda et al, 1994;Ouimet et al, 1994;Trapp and Hauer, 1994) but because antibodies raised against independent epitopes of APP cross-react with APLP2 (Slunt et al, 1994), it is quite likely that the distributions of APP IR described in a variety of reports, including our own (Martin et al, 1991) reflect IR to APP, APLP2, and perhaps APLPl, as well. To define the distribution of APLP2 in the CNS, we generated a series of antibodies against nonoverlapping epitopes of mouse APLP2.…”

Section: Discussionmentioning

confidence: 93%

Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis

et al. 1995

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Deposition of beta-amyloid (A beta) in senile plaques is a major pathological characteristic of Alzheimer's disease. A beta is generated by proteolytic processing of amyloid precursor proteins (APP). APP is a member of a family of related polypeptides that includes amyloid precursor-like proteins APLP1 and APLP2. To examine the distribution of APLP2 in the nervous system, we generated antibodies specific for APLP2 and used these reagents in immunocytochemical and biochemical studies of the rodent nervous system. In this report, we document that in cortex and hippocampus, APLP2 is enriched in postsynaptic compartments. In the olfactory system, however, APLP2 is abundant in olfactory sensory axons, and axon terminals in glomeruli. Confocal microscopy revealed that APLP2 is present in both pre- and postsynaptic compartments in the olfactory bulb. Notably, mRNA encoding chondroitin sulfate glycosaminoglycan (CS GAG)-modified forms of APLP2 are enriched in the olfactory epithelium, relative to alternatively-spliced mRNA, encoding CS GAG-free forms of APLP2. In addition, we demonstrate that CS-modified APLP2 forms accumulate in the olfactory bulb. CS proteoglycans are known to play an important role in regulating cell migration and neuronal outgrowth. Since sensory neurons in the olfactory epithelium are in a state of continual turnover, axons of newly generated cells must establish synaptic connections with neurons in the olfactory bulb in adult life. The presence of APLP2 in olfactory sensory axons and glomeruli is consistent with the view that this protein may play an important role in axonal pathfinding and/or synaptogenesis.

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Section: Discussionmentioning

confidence: 93%

Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis

et al. 1995

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“…Finally, senile plaques do not appear to progress beyond the diffuse plaque stage. Most investigators have been unable to detect later‐stage thioflavine‐ or Congo red‐positive plaques in canine brains (Giaccone et al, ; Uchida et al, ; Okuda et al, ). On the other hand, classic/neuritic plaques stained either by the silver method or by Congo red have been observed in some previous studies of the canine brain (Russell et al, ; Shimada et al, ; Rofina et al, ).…”

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confidence: 99%

Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment

Smolek

Maďari

Farbáková

et al. 2015

J of Comparative Neurology

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Canine cognitive impairment syndrome (CDS) represents a group of symptoms related to the aging of the canine brain. These changes ultimately lead to a decline of memory function and learning abilities, alteration of social interaction, impairment of normal housetraining, and changes in sleep-wake cycle and general activity. We have clinically examined 215 dogs, 28 of which underwent autopsy. With canine brains, we performed extensive analysis of pathological abnormalities characteristic of human Alzheimer's disease and frontotemporal lobar degeneration, including β-amyloid senile plaques, tau neurofibrillary tangles, and fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP43) inclusions. Most demented dogs displayed senile plaques, mainly in the frontal and temporal cortex. Tau neurofibrillary inclusions were found in only one dog. They were identified with antibodies used to detect tau neurofibrillary lesions in the human brain. The inclusions were also positive for Gallyas silver staining. As in humans, they were distributed mainly in the entorhinal cortex, hippocampus, and temporal cortex. On the other hand, FUS and TDP43 aggregates were not present in any of the examined brain samples. We also found that CDS was characterized by the presence of reactive and senescent microglial cells in the frontal cortex. Our transcriptomic study revealed a significant dysregulation of genes involved in neuroinflammation. Finally, we analyzed tau phosphoproteome in the synaptosomes. Proteomic studies revealed a significant increase of hyperphosphorylated tau in synaptosomes of demented dogs compared with nondemented dogs. This study suggests that cognitive decline in dogs is related to the tau synaptic impairment and neuroinflammation. J. Comp. Neurol. 524:874-895, 2016. © 2015 Wiley Periodicals, Inc.

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“…Canine CSF contains A/3 that is simi!ar in abundance (Seubert et a!., 1992) and identical in sequence to human A/3 (Johnstone et al, 1991). Amy!oid plaques have been observed in aged canine brain (Cummings et a!., 1993;Okuda et al, 1994) and A/3 accumulation has been correlated with cognitive deficits in aged canines (Cummings et al, 1996). Quantitation was accomplished using a sensitive western blot assay that used radiolabe!ed secondary antibody to detect an epitope common to A/3 and so!uble APP, and a capture ELISA assay that measured soluble A~3.We found that zinc induced selective aggregation of both soluble A/3 and APP,.…”

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confidence: 99%

Selective Aggregation of Endogenous β‐Amyloid Peptide and Soluble Amyloid Precursor Protein in Cerebrospinal Fluid by Zinc

Brown¹,

Tummolo²,

Rhodes³

et al. 1997

Journal of Neurochemistry

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Zinc added to buffered solutions of synthetic β‐amyloid peptide (Aβ) has been reported to induce accelerated formation of insoluble aggregates. This observation suggests that zinc may play a role in the formation of senile plaques, which contain Aβ, in Alzheimer's disease. To test this hypothesis under conditions more representative of the brain, we investigated the ability of zinc to induce aggregation of Aβ in freshly drawn canine CSF, which contains the same sequence as human Aβ. Aggregates were separated from CSF by ultracentrifugation before and after incubation with zinc and assayed by quantitative western blotting and ELISA. We found that zinc induced the rapid aggregation of endogenous Aβ in CSF, with an EC50 of 120–140 µM. The reaction was specific, because most (≥95%) CSF protein remained soluble under conditions where most Aβ was insoluble, as assayed by scanning densitometry of Coomassie‐stained gels. Staining of the precipitated material resulted in the visualization of punctate regions that were thioflavin positive or birefringent when stained with Congo red, suggesting the formation of amyloid‐related structures. These results suggest that zinc could play a role in amyloid deposition, because there is overlap between the regions of the brain where zinc concentrations are highest and regions with the highest amyloid content. It is surprising that zinc induced the aggregation of endogenous soluble APP at lower concentrations than required for Aβ (EC50 80 µM). The possibility that zinc‐induced aggregation of APP may precede the deposition of Aβ into plaques is discussed. Investigation of aggregation of Aβ in CSF will aid in assessing the biological relevance of other agents that have been reported to accelerate amyloid formation.

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The distribution of amyloid beta precursor protein in canine brain

Cited by 3 publications

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Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis

Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis

Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment

Selective Aggregation of Endogenous β‐Amyloid Peptide and Soluble Amyloid Precursor Protein in Cerebrospinal Fluid by Zinc

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