{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["18"],"submitter":["Maksour S"],"pubmed_abstract":["Alzheimer's disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in <i>PSEN1</i> (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD progression, the link between <i>PSEN1</i> mutations and neuronal excitability remains to be fully elucidated. This study examined iPSC-derived neurons (iNs) from fAD patients with <i>PSEN1</i> mutations S290C or A246E, alongside CRISPR-corrected isogenic cell lines, to investigate early changes in excitability. Electrophysiological profiling revealed reduced excitability in both <i>PSEN1</i> mutant iNs compared to their isogenic controls. Neurons bearing S290C and A246E mutations exhibited divergent passive membrane properties compared to isogenic controls, suggesting distinct effects of <i>PSEN1</i> mutations on neuronal excitability. Additionally, both <i>PSEN1</i> backgrounds exhibited higher current density of voltage-gated potassium (Kv) channels relative to their isogenic iNs, while displaying comparable voltage-gated sodium (Nav) channel current density. This suggests that the Nav/Kv imbalance contributes to impaired neuronal firing in fAD iNs. Deciphering these early cellular and molecular changes in AD is crucial for understanding disease pathogenesis."],"journal":["Frontiers in cellular neuroscience"],"pagination":["1406970"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11497635"],"repository":["biostudies-literature"],"pubmed_title":["Alzheimer's disease induced neurons bearing &lt;i&gt;PSEN1&lt;/i&gt; mutations exhibit reduced excitability."],"pmcid":["PMC11497635"],"pubmed_authors":["Sidhu K","Sanz Munoz S","Sachdev PS","Berg T","Cabral-da-Silva MEC","Turner C","Engel M","Lisowski L","Dottori M","Maksour S","Hulme AJ","Finol-Urdaneta RK","Balez R","Ooi L","Kalajdzic P","Targa Dias Anastacio H"],"additional_accession":[]},"is_claimable":false,"name":"Alzheimer's disease induced neurons bearing &lt;i&gt;PSEN1&lt;/i&gt; mutations exhibit reduced excitability.","description":"Alzheimer's disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in <i>PSEN1</i> (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD progression, the link between <i>PSEN1</i> mutations and neuronal excitability remains to be fully elucidated. This study examined iPSC-derived neurons (iNs) from fAD patients with <i>PSEN1</i> mutations S290C or A246E, alongside CRISPR-corrected isogenic cell lines, to investigate early changes in excitability. Electrophysiological profiling revealed reduced excitability in both <i>PSEN1</i> mutant iNs compared to their isogenic controls. Neurons bearing S290C and A246E mutations exhibited divergent passive membrane properties compared to isogenic controls, suggesting distinct effects of <i>PSEN1</i> mutations on neuronal excitability. Additionally, both <i>PSEN1</i> backgrounds exhibited higher current density of voltage-gated potassium (Kv) channels relative to their isogenic iNs, while displaying comparable voltage-gated sodium (Nav) channel current density. This suggests that the Nav/Kv imbalance contributes to impaired neuronal firing in fAD iNs. Deciphering these early cellular and molecular changes in AD is crucial for understanding disease pathogenesis.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2025-04-22T09:40:25.714Z","creation":"2025-04-05T23:11:31.813Z"},"accession":"S-EPMC11497635","cross_references":{"pubmed":["39444394"],"doi":["10.3389/fncel.2024.1406970"]}}