Aberrant accentuation of neurofibrillary degeneration in the hippocampus of Alzheimer's disease with amyloid precursor protein 717 and presenilin-1 gene mutations.
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.
Sudo
Satoru
S
Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka-cho, Fukui 910-1193, Japan. satorv@fmsrsa.fukui-med.ac.jp
Shiozawa
Masaki
M
Cairns
Nigel J
NJ
Wada
Yuji
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D053764:Presenilin-1; D013223:Statistics as Topic / Q000379:methods
C094559:APP717; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1