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Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology

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Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology. / Kar, S.; Poirier, J.; Guevara, J.; Dea, D.; Hawkes, C.; Robitaille, Y.; Quirion, R.

In: Neurobiology of Aging, Vol. 27, No. 2, 01.02.2006, p. 199-210.

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Kar, S. ; Poirier, J. ; Guevara, J. ; Dea, D. ; Hawkes, C. ; Robitaille, Y. ; Quirion, R. / Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology. In: Neurobiology of Aging. 2006 ; Vol. 27, No. 2. pp. 199-210.

Bibtex

@article{5c44222697734181aa3f02e5958e873e,
title = "Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology",
abstract = "The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional membrane glycoprotein, which binds different classes of ligands including IGF-II and M6P-bearing lysosomal enzymes. Besides participating in the process of endocytosis this receptor functions in the trafficking of lysosomal enzymes from the trans-Glogi network (TGN) or the cell surface to lysosomes. In Alzheimer's disease (AD) brain, marked overexpression of certain lysosomal enzymes in vulnerable neuronal populations and their association to β-amyloid (Aβ) containing neuritic plaques has been correlated to altered metabolic functions. In the present study, we measured the levels of IGF-II/M6P receptor and characterized its distribution profile in selected regions of AD and age-matched normal postmortem brains. Western blot analysis revealed no significant alteration in the levels of IGF-II/M6P receptor either in the hippocampus, frontal cortex or cerebellum between AD and age-matched control brains. However, a significant gene dose effect of apolipoprotein E (APOE) ε4 allele on IGF-II/M6P receptor levels was evident in the hippocampus of the AD brain. At the cellular level, immunoreactive IGF-II/M6P receptors were localized in the neurons of the frontal cortex, hippocampus and cerebellum of control brains. In AD brains, the labeling of the neurons was less intense in the frontal cortex and hippocampus than in the age-matched control brains. Additionally, IGF-II/M6P receptor immunoreactivity was observed in association with a subpopulation of Aβ-containing neuritic plaques as well as tau-positive neurofibrillary tangles both in the frontal cortex and the hippocampus. Reactive glial cells localized adjacent to the plaques also occasionally exhibited IGF-II/M6P receptor immunoreactivity. These results, when analyzed in context of the established role of the IGF-II/M6P receptor in the regulation of the intracellular trafficking of lysosomal enzymes, suggest that alterations in IGF-II/M6P receptor levels/distribution are possibly associated with altered functioning of the lysosomal enzymes and/or loss of neurons observed in AD brains, especially in patients carrying APOE ε4 alleles.",
keywords = "β-Amyloid, Endosomal-lysosomal system, Neuritic plaques, Neurodegeneration, Neurofibrillary tangles",
author = "S. Kar and J. Poirier and J. Guevara and D. Dea and C. Hawkes and Y. Robitaille and R. Quirion",
year = "2006",
month = feb,
day = "1",
doi = "10.1016/j.neurobiolaging.2005.03.005",
language = "English",
volume = "27",
pages = "199--210",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology

AU - Kar, S.

AU - Poirier, J.

AU - Guevara, J.

AU - Dea, D.

AU - Hawkes, C.

AU - Robitaille, Y.

AU - Quirion, R.

PY - 2006/2/1

Y1 - 2006/2/1

N2 - The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional membrane glycoprotein, which binds different classes of ligands including IGF-II and M6P-bearing lysosomal enzymes. Besides participating in the process of endocytosis this receptor functions in the trafficking of lysosomal enzymes from the trans-Glogi network (TGN) or the cell surface to lysosomes. In Alzheimer's disease (AD) brain, marked overexpression of certain lysosomal enzymes in vulnerable neuronal populations and their association to β-amyloid (Aβ) containing neuritic plaques has been correlated to altered metabolic functions. In the present study, we measured the levels of IGF-II/M6P receptor and characterized its distribution profile in selected regions of AD and age-matched normal postmortem brains. Western blot analysis revealed no significant alteration in the levels of IGF-II/M6P receptor either in the hippocampus, frontal cortex or cerebellum between AD and age-matched control brains. However, a significant gene dose effect of apolipoprotein E (APOE) ε4 allele on IGF-II/M6P receptor levels was evident in the hippocampus of the AD brain. At the cellular level, immunoreactive IGF-II/M6P receptors were localized in the neurons of the frontal cortex, hippocampus and cerebellum of control brains. In AD brains, the labeling of the neurons was less intense in the frontal cortex and hippocampus than in the age-matched control brains. Additionally, IGF-II/M6P receptor immunoreactivity was observed in association with a subpopulation of Aβ-containing neuritic plaques as well as tau-positive neurofibrillary tangles both in the frontal cortex and the hippocampus. Reactive glial cells localized adjacent to the plaques also occasionally exhibited IGF-II/M6P receptor immunoreactivity. These results, when analyzed in context of the established role of the IGF-II/M6P receptor in the regulation of the intracellular trafficking of lysosomal enzymes, suggest that alterations in IGF-II/M6P receptor levels/distribution are possibly associated with altered functioning of the lysosomal enzymes and/or loss of neurons observed in AD brains, especially in patients carrying APOE ε4 alleles.

AB - The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional membrane glycoprotein, which binds different classes of ligands including IGF-II and M6P-bearing lysosomal enzymes. Besides participating in the process of endocytosis this receptor functions in the trafficking of lysosomal enzymes from the trans-Glogi network (TGN) or the cell surface to lysosomes. In Alzheimer's disease (AD) brain, marked overexpression of certain lysosomal enzymes in vulnerable neuronal populations and their association to β-amyloid (Aβ) containing neuritic plaques has been correlated to altered metabolic functions. In the present study, we measured the levels of IGF-II/M6P receptor and characterized its distribution profile in selected regions of AD and age-matched normal postmortem brains. Western blot analysis revealed no significant alteration in the levels of IGF-II/M6P receptor either in the hippocampus, frontal cortex or cerebellum between AD and age-matched control brains. However, a significant gene dose effect of apolipoprotein E (APOE) ε4 allele on IGF-II/M6P receptor levels was evident in the hippocampus of the AD brain. At the cellular level, immunoreactive IGF-II/M6P receptors were localized in the neurons of the frontal cortex, hippocampus and cerebellum of control brains. In AD brains, the labeling of the neurons was less intense in the frontal cortex and hippocampus than in the age-matched control brains. Additionally, IGF-II/M6P receptor immunoreactivity was observed in association with a subpopulation of Aβ-containing neuritic plaques as well as tau-positive neurofibrillary tangles both in the frontal cortex and the hippocampus. Reactive glial cells localized adjacent to the plaques also occasionally exhibited IGF-II/M6P receptor immunoreactivity. These results, when analyzed in context of the established role of the IGF-II/M6P receptor in the regulation of the intracellular trafficking of lysosomal enzymes, suggest that alterations in IGF-II/M6P receptor levels/distribution are possibly associated with altered functioning of the lysosomal enzymes and/or loss of neurons observed in AD brains, especially in patients carrying APOE ε4 alleles.

KW - β-Amyloid

KW - Endosomal-lysosomal system

KW - Neuritic plaques

KW - Neurodegeneration

KW - Neurofibrillary tangles

U2 - 10.1016/j.neurobiolaging.2005.03.005

DO - 10.1016/j.neurobiolaging.2005.03.005

M3 - Journal article

C2 - 16399207

AN - SCOPUS:29844439691

VL - 27

SP - 199

EP - 210

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 2

ER -