Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study

Hansson, Oskar; Zetterberg, Henrik; Buchhave, Peder; Londos, Elisabet; Blennow, Kaj; Minthon, Lennart

doi:10.1016/s1474-4422(06)70355-6

Cited by 1,515 publications

(1,304 citation statements)

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“…One would expect, for example, high-affinity chelators to inhibit Aβ degradation if they could enter the CSF compartment. This could be viewed a favorable since low CSF Aβ levels have predictive value for developing AD [17,41]. However treatment with clioquinol (CQ), a zinc/copper chelator, lowered plasma Aβ in a double-blind phase 2 pilot study in AD subjects [38].…”

Section: Discussionmentioning

confidence: 99%

Zinc and copper modulate Alzheimer Aβ levels in human cerebrospinal fluid

Strozyk

Launer

Adlard

et al. 2009

Neurobiology of Aging

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137

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Abnormal interaction of β-amyloid 42 (Aβ42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, Aβ degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Aβ and biological metals in CSF. We assayed CSF copper, zinc, other metals and Aβ42 in ventricular autopsy samples of Japanese American men (N= 131) from the population-based Honolulu-Asia Aging Study. There was a significant inverse correlation of CSF Aβ42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF Aβ42. In vitro, the degradation of synthetic Aβ substrate added to CSF was markedly accelerated by low levels (2 μM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Aβ precipitation in AD, soluble Aβ degradation is normally promoted by physiological copper and zinc concentrations.

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Section: Discussionmentioning

confidence: 99%

Zinc and copper modulate Alzheimer Aβ levels in human cerebrospinal fluid

Strozyk

Launer

Adlard

et al. 2009

Neurobiology of Aging

Self Cite

137

View full text Add to dashboard Cite

show abstract

“…The levels of total tau, tau phosphorylated at Thr 181 (Ptau) and β-amyloid 1-42 (Aβ42) were determined using xMAP technology as previously described [17,28]. Briefly, this technology is based on flow cytometric separation of antibodycoated microspheres, which are labelled with a mixture of two fluorescent dyes.…”

Section: Analysis Of Baseline Csfmentioning

confidence: 99%

“…The cerebrospinal fluid (CSF) biomarkers tau and β-amyloid 1-42 (Aβ42) can be used to detect preclinical AD in MCI populations with relatively high diagnostic accuracy [4,15,17].…”

Section: Introductionmentioning

confidence: 99%

“…Cerebrospinal fluid tau and Aβ42 are markers of the underlying molecular disease process and they seem to be altered very early in the neuropathological process [4,17]. However, these CSF biomarkers do not seem to predict the rate of disease progression, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…they are equally changed in MCI subjects who will develop AD within one year as in patients who will convert to AD after e.g. three years [17].…”

Section: Introductionmentioning

confidence: 99%

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