CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer's disease

Giacomo Koch, Francesco Di Lorenzo, Stefano Loizzo, Caterina Motta, Sara Travaglione, Monica Baiula, Roberto Rimondini, Viviana Ponzo, Sonia Bonnì, Sofia Toniolo, Fabrizio Sallustio, Marco Bozzali, Carlo Caltagirone, Gabriele Campana, Alessandro Martorana

Research output: Contribution to journalArticle

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Abstract

In Alzheimer's disease (AD) patients, apopoliprotein (APOE) polymorphism is the main genetic factor associated with more aggressive clinical course. However, the interaction between cerebrospinal fluid (CSF) tau protein levels and APOE genotype has been scarcely investigated. A possible key mechanism invokes the dysfunction of synaptic plasticity. We investigated how CSF tau interacts with APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE genotype influence disease progression and long-term potentiation (LTP)-like cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD patients. Then, we incubated normal human astrocytes (NHAs) with CSF collected from sub-groups of AD patients to determine whether APOE genotype and CSF biomarkers influence astrocytes survival. LTP-like cortical plasticity differed between AD patients with apolipoprotein E4 (APOE4) and apolipoprotein E3 (APOE3) genotype. Higher CSF tau levels were associated with more impaired LTP-like cortical plasticity and faster disease progression in AD patients with APOE4 but not APOE3 genotype. Apoptotic activity was higher when cells were incubated with CSF from AD patients with APOE4 and high tau levels. CSF tau is detrimental on cortical plasticity, disease progression and astrocyte survival only when associated with APOE4 genotype. This is relevant for new therapeutic approaches targeting tau.

Original languageEnglish
Pages (from-to)13728
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Oct 23 2017

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Apolipoprotein E4
Astrocytes
Cerebrospinal Fluid
Alzheimer Disease
Genotype
Long-Term Potentiation
Apolipoprotein E3
Disease Progression
Cerebrospinal Fluid Proteins
tau Proteins
Neuronal Plasticity
Transcranial Magnetic Stimulation
Cognitive Dysfunction
Biomarkers

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CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer's disease. / Koch, Giacomo; Di Lorenzo, Francesco; Loizzo, Stefano; Motta, Caterina; Travaglione, Sara; Baiula, Monica; Rimondini, Roberto; Ponzo, Viviana; Bonnì, Sonia; Toniolo, Sofia; Sallustio, Fabrizio; Bozzali, Marco; Caltagirone, Carlo; Campana, Gabriele; Martorana, Alessandro.

In: Scientific Reports, Vol. 7, No. 1, 23.10.2017, p. 13728.

Research output: Contribution to journalArticle

Koch, G, Di Lorenzo, F, Loizzo, S, Motta, C, Travaglione, S, Baiula, M, Rimondini, R, Ponzo, V, Bonnì, S, Toniolo, S, Sallustio, F, Bozzali, M, Caltagirone, C, Campana, G & Martorana, A 2017, 'CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer's disease', Scientific Reports, vol. 7, no. 1, pp. 13728. https://doi.org/10.1038/s41598-017-14204-3
Koch, Giacomo ; Di Lorenzo, Francesco ; Loizzo, Stefano ; Motta, Caterina ; Travaglione, Sara ; Baiula, Monica ; Rimondini, Roberto ; Ponzo, Viviana ; Bonnì, Sonia ; Toniolo, Sofia ; Sallustio, Fabrizio ; Bozzali, Marco ; Caltagirone, Carlo ; Campana, Gabriele ; Martorana, Alessandro. / CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer's disease. In: Scientific Reports. 2017 ; Vol. 7, No. 1. pp. 13728.
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AB - In Alzheimer's disease (AD) patients, apopoliprotein (APOE) polymorphism is the main genetic factor associated with more aggressive clinical course. However, the interaction between cerebrospinal fluid (CSF) tau protein levels and APOE genotype has been scarcely investigated. A possible key mechanism invokes the dysfunction of synaptic plasticity. We investigated how CSF tau interacts with APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE genotype influence disease progression and long-term potentiation (LTP)-like cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD patients. Then, we incubated normal human astrocytes (NHAs) with CSF collected from sub-groups of AD patients to determine whether APOE genotype and CSF biomarkers influence astrocytes survival. LTP-like cortical plasticity differed between AD patients with apolipoprotein E4 (APOE4) and apolipoprotein E3 (APOE3) genotype. Higher CSF tau levels were associated with more impaired LTP-like cortical plasticity and faster disease progression in AD patients with APOE4 but not APOE3 genotype. Apoptotic activity was higher when cells were incubated with CSF from AD patients with APOE4 and high tau levels. CSF tau is detrimental on cortical plasticity, disease progression and astrocyte survival only when associated with APOE4 genotype. This is relevant for new therapeutic approaches targeting tau.

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