CSF Rau is associateed with impaired cortical plasticity, cognitive decline and astrocyte survival.pdf (1.96 MB)
CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer's disease
journal contribution
posted on 2023-06-09, 13:14 authored by 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 MartoranaIn 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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Publication status
- Published
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- Published version
Journal
Scientific ReportsISSN
2045-2322Publisher
Nature ResearchExternal DOI
Issue
13728Volume
7Page range
1-12Department affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-05-14First Open Access (FOA) Date
2019-05-14First Compliant Deposit (FCD) Date
2019-05-14Usage metrics
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