Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease

Minthon, Lennart LU ; Hesse, Camilla ; Sjogren, Magnus ; Englund, Elisabeth ; Gustafson, Lars LU and Blennow, Kaj (1997) In Neuroscience Letters 226(1). p.65-68
Abstract
The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated... (More)
The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P < 0.01) in FTD patients possessing the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuroscience Letters
volume
226
issue
1
pages
65 - 68
publisher
Elsevier
external identifiers
  • scopus:0030610527
ISSN
0304-3940
DOI
10.1016/S0304-3940(97)00230-9
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Psychogeriatrics (013304000), Clinical Memory Research Unit (013242610)
id
692373e4-09a3-44f0-aca7-73bd81f4d4ff (old id 1296444)
date added to LUP
2016-04-01 12:37:47
date last changed
2022-01-27 07:39:31
@article{692373e4-09a3-44f0-aca7-73bd81f4d4ff,
  abstract     = {{The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P &lt; 0.01) in FTD patients possessing the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD.}},
  author       = {{Minthon, Lennart and Hesse, Camilla and Sjogren, Magnus and Englund, Elisabeth and Gustafson, Lars and Blennow, Kaj}},
  issn         = {{0304-3940}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{65--68}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience Letters}},
  title        = {{The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease}},
  url          = {{http://dx.doi.org/10.1016/S0304-3940(97)00230-9}},
  doi          = {{10.1016/S0304-3940(97)00230-9}},
  volume       = {{226}},
  year         = {{1997}},
}