| Aberrant accentuation of neurofibrillary degeneration in the hippocampus of Alzheimer's disease with amyloid precursor protein 717 and presenilin-1 gene mutations. | |
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MedLine Citation:
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PMID: 15946688 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study reports correlation of the hippocampal neurofibrillary tangles (NFT) density with beta-amyloid (Abeta) precursor protein (APP) 717 mutation, presenilin (PS)-1 mutation and apolipoprotein E (Apo-E) e4 alleles (E4), being graded as 3 forms (no-E4, one-E4 and two-E4) in autopsied brains from patients with familial and non-familial Alzheimer's disease (AD). We studied the density of NFT-free neurons, intracellular NFT (I-NFT), extracellular NFT (E-NFT) and total NFT (I-NFT plus E-NFT) in the six hippocampal subdivisions: cornu ammonis (CA) 1-CA4, subiculum and entorhinal cortex. The APP mutation cases showed significantly higher total NFT density in the CA1-CA2 region, and the PS-1 mutation cases also showed higher density of total NFT in the CA1-CA3 than non-familial cases. Moreover, high densities of the E-NFT contributed to these high total NFT densities. Non-familial AD cases showed a stereotypical NFT distribution with entorhinal accentuation in the hippocampus irrespective of E4 frequency. Thus, APP and PS-1 mutations predominantly affect the CA regions with profound neurodegeneration, which contributes early and severe clinical features of familial AD. |
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Authors:
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Satoru Sudo; Masaki Shiozawa; Nigel J Cairns; Yuji Wada |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the neurological sciences Volume: 234 ISSN: 0022-510X ISO Abbreviation: J. Neurol. Sci. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-07-04 Completed Date: 2005-09-19 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375403 Medline TA: J Neurol Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 55-65 Citation Subset: IM |
Affiliation:
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Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka-cho, Fukui 910-1193, Japan. satorv@fmsrsa.fukui-med.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Alzheimer Disease / genetics*, pathology Amyloid beta-Protein Precursor / genetics* Analysis of Variance Apolipoprotein E4 Apolipoproteins E / genetics DNA Mutational Analysis / methods Female Hippocampus / cytology, pathology* Humans Male Membrane Proteins / genetics* Middle Aged Neurofibrillary Tangles / genetics, pathology* Neurons / pathology Presenilin-1 Statistics as Topic / methods |
| Chemical | |
Reg. No./Substance:
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0/APP717; 0/Amyloid beta-Protein Precursor; 0/Apolipoprotein E4; 0/Apolipoproteins E; 0/Membrane Proteins; 0/PSEN1 protein, human; 0/Presenilin-1 |
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