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Neuropathology of mice carrying mutant APP(swe) and/or PS1(M146L) transgenes: alterations in the p75(NTR) cholinergic basal forebrain septohippocampal pathway.
Exp Neurol 2001; 170(2):227-43EN

Abstract

Cholinergic basal forebrain (CBF) projection systems are defective in late Alzheimer's disease (AD). We examined the brains of 12-month-old singly and doubly transgenic mice overexpressing mutant amyloid precursor protein (APP(swe)) and/or presenilin-1 (PS1(M146L)) to investigate the effects of these AD-related genes on plaque and tangle pathology, astrocytic expression, and the CBF projection system. Two types of beta-amyloid (Abeta)-immunoreactive (ir) plaques were observed: type 1 were darkly stained oval and elongated deposits of Abeta, and type 2 were diffuse plaques containing amyloid fibrils. APP(swe) and PS1(M146L) mouse brains contained some type 1 plaques, while the doubly transgenic (APP(swe)/PS1(M146L)) mice displayed a greater abundance of types 1 and 2 plaques. Sections immunostained for the p75 NGF receptor (p75(NTR)) revealed circular patches scattered throughout the cortex and hippocampus of the APP(swe)/PS1(M146L) mice that contained Abeta, were innervated by p75(NTR)-ir neurites, but displayed virtually no immunopositive neurons. Tau pathology was not seen in any transgenic genotype, although a massive glial response occurred in the APP(swe)/PS1(M146L) mice associated with amyloid plaques. Stereology revealed a significant increase in p75(NTR)-ir medial septal neurons in the APP(swe) and PS1(M146L) singly transgenic mice compared to the APP(swe)/PS1(M146L) mice. No differences in size or optical density of p75(NTR)-ir neurons were observed in these three mutants. p75(NTR)-ir fibers in hippocampus and cortex were more pronounced in the APP(swe) and PS1(M146L) mice, while the APP(swe)/PS1(M146L) mice showed the least p75(NTR)-ir fiber staining. These findings suggest a neurotrophic role for mutant APP and PS1 upon cholinergic hippocampal projection neurons at 12 months of age.

Authors+Show Affiliations

Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11476589

Citation

Jaffar, S, et al. "Neuropathology of Mice Carrying Mutant APP(swe) And/or PS1(M146L) Transgenes: Alterations in the p75(NTR) Cholinergic Basal Forebrain Septohippocampal Pathway." Experimental Neurology, vol. 170, no. 2, 2001, pp. 227-43.
Jaffar S, Counts SE, Ma SY, et al. Neuropathology of mice carrying mutant APP(swe) and/or PS1(M146L) transgenes: alterations in the p75(NTR) cholinergic basal forebrain septohippocampal pathway. Exp Neurol. 2001;170(2):227-43.
Jaffar, S., Counts, S. E., Ma, S. Y., Dadko, E., Gordon, M. N., Morgan, D., & Mufson, E. J. (2001). Neuropathology of mice carrying mutant APP(swe) and/or PS1(M146L) transgenes: alterations in the p75(NTR) cholinergic basal forebrain septohippocampal pathway. Experimental Neurology, 170(2), pp. 227-43.
Jaffar S, et al. Neuropathology of Mice Carrying Mutant APP(swe) And/or PS1(M146L) Transgenes: Alterations in the p75(NTR) Cholinergic Basal Forebrain Septohippocampal Pathway. Exp Neurol. 2001;170(2):227-43. PubMed PMID: 11476589.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropathology of mice carrying mutant APP(swe) and/or PS1(M146L) transgenes: alterations in the p75(NTR) cholinergic basal forebrain septohippocampal pathway. AU - Jaffar,S, AU - Counts,S E, AU - Ma,S Y, AU - Dadko,E, AU - Gordon,M N, AU - Morgan,D, AU - Mufson,E J, PY - 2001/7/31/pubmed PY - 2001/9/14/medline PY - 2001/7/31/entrez SP - 227 EP - 43 JF - Experimental neurology JO - Exp. Neurol. VL - 170 IS - 2 N2 - Cholinergic basal forebrain (CBF) projection systems are defective in late Alzheimer's disease (AD). We examined the brains of 12-month-old singly and doubly transgenic mice overexpressing mutant amyloid precursor protein (APP(swe)) and/or presenilin-1 (PS1(M146L)) to investigate the effects of these AD-related genes on plaque and tangle pathology, astrocytic expression, and the CBF projection system. Two types of beta-amyloid (Abeta)-immunoreactive (ir) plaques were observed: type 1 were darkly stained oval and elongated deposits of Abeta, and type 2 were diffuse plaques containing amyloid fibrils. APP(swe) and PS1(M146L) mouse brains contained some type 1 plaques, while the doubly transgenic (APP(swe)/PS1(M146L)) mice displayed a greater abundance of types 1 and 2 plaques. Sections immunostained for the p75 NGF receptor (p75(NTR)) revealed circular patches scattered throughout the cortex and hippocampus of the APP(swe)/PS1(M146L) mice that contained Abeta, were innervated by p75(NTR)-ir neurites, but displayed virtually no immunopositive neurons. Tau pathology was not seen in any transgenic genotype, although a massive glial response occurred in the APP(swe)/PS1(M146L) mice associated with amyloid plaques. Stereology revealed a significant increase in p75(NTR)-ir medial septal neurons in the APP(swe) and PS1(M146L) singly transgenic mice compared to the APP(swe)/PS1(M146L) mice. No differences in size or optical density of p75(NTR)-ir neurons were observed in these three mutants. p75(NTR)-ir fibers in hippocampus and cortex were more pronounced in the APP(swe) and PS1(M146L) mice, while the APP(swe)/PS1(M146L) mice showed the least p75(NTR)-ir fiber staining. These findings suggest a neurotrophic role for mutant APP and PS1 upon cholinergic hippocampal projection neurons at 12 months of age. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/11476589/Neuropathology_of_mice_carrying_mutant_APP_swe__and/or_PS1_M146L__transgenes:_alterations_in_the_p75_NTR__cholinergic_basal_forebrain_septohippocampal_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(01)97710-6 DB - PRIME DP - Unbound Medicine ER -