Document Detail


Aberrant accentuation of neurofibrillary degeneration in the hippocampus of Alzheimer's disease with amyloid precursor protein 717 and presenilin-1 gene mutations.
MedLine Citation:
PMID:  15946688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Satoru Sudo; Masaki Shiozawa; Nigel J Cairns; Yuji Wada
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the neurological sciences     Volume:  234     ISSN:  0022-510X     ISO Abbreviation:  J. Neurol. Sci.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-04     Completed Date:  2005-09-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375403     Medline TA:  J Neurol Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  55-65     Citation Subset:  IM    
Affiliation:
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:
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:
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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