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Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients

Olsson, A; Hoglund, K; Sjogren, M; Andreasen, N; Minthon, Lennart LU ; Lannfelt, L; Buerger, K; Moller, HJ; Hampel, H and Davidsson, P, et al. (2003) In Experimental Neurology 183(1). p.74-80
Abstract
One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These... (More)
One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved. (Less)
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keywords
cerebrospinal fluid, beta-amyloid, apolipoprotein E, Alzheimer's disease, amyloid precursor protein, ELISA, mild cognitive impairment, secretase
in
Experimental Neurology
volume
183
issue
1
pages
74 - 80
publisher
Academic Press
external identifiers
  • wos:000185166700010
  • pmid:12957490
  • scopus:0041886881
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0014-4886
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English
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yes
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50d6a367-5ed8-43d5-9ea8-d2294e108a23 (old id 301753)
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2007-09-19 15:30:38
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2018-06-17 03:57:41
@article{50d6a367-5ed8-43d5-9ea8-d2294e108a23,
  abstract     = {One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.},
  author       = {Olsson, A and Hoglund, K and Sjogren, M and Andreasen, N and Minthon, Lennart and Lannfelt, L and Buerger, K and Moller, HJ and Hampel, H and Davidsson, P and Blennow, K},
  issn         = {0014-4886},
  keyword      = {cerebrospinal fluid,beta-amyloid,apolipoprotein E,Alzheimer's disease,amyloid precursor protein,ELISA,mild cognitive impairment,secretase},
  language     = {eng},
  number       = {1},
  pages        = {74--80},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients},
  url          = {http://dx.doi.org/},
  volume       = {183},
  year         = {2003},
}