{"id":2417,"date":"2025-12-01T02:57:02","date_gmt":"2025-12-01T02:57:02","guid":{"rendered":"https:\/\/antoniosdougalis.com\/?p=2417"},"modified":"2025-12-01T03:09:21","modified_gmt":"2025-12-01T03:09:21","slug":"neurons-fire-in-early-alzheimers-linking-electrophysiology-to-microglial-states","status":"publish","type":"post","link":"https:\/\/antoniosdougalis.com\/?p=2417","title":{"rendered":"NEURONS FIRE IN EARLY ALZHEIMER&#8217;S LINKING ELECTROPHYSIOLOGY TO MICROGLIAL STATES"},"content":{"rendered":"\n<div class=\"wp-block-group is-nowrap is-layout-flex wp-container-core-group-is-layout-ad2f72ca wp-block-group-is-layout-flex\">\n<p>A commentary on how Neurons fire in Early Alzheimer\u2019s: Linking Electrophysiology to Microglial States<br><br>A few days ago the <a href=\"https:\/\/www.linkedin.com\/company\/alzforum\/\">Alzforum<\/a> covered again my recent work and its relation to ongoing work in the field of immunology after news emerged following the Alzheimer\u2019s Association International Conference in Toronto<\/p>\n<\/div>\n\n\n\n<p>My latest work (Dougalis et al., 2025, <a href=\"https:\/\/www.biorxiv.org\/content\/10.1101\/2025.01.07.630516v1.full\">https:\/\/www.biorxiv.org\/content\/10.1101\/2025.01.07.630516v1.full<\/a>) is diving into the electrophysiological consequences of early Alzheimer\u2019s pathology in human neurons\u2014and the findings are striking. By recording from layer 2\/3 pyramidal neurons in iNPH biopsy tissue, we\u2019ve shown that amyloid and tau pathology reshape the electrical behavior of these cells while inhibitory control from layer 1 neurons falters. This gives a direct window into how pathology disrupts neuronal network function.<br><br>At the recent Alzheimer\u2019s Association International Conference in Toronto, researchers from the iNPH cohort highlighted complementary insights:<br><br>Disease-associated microglia (DAMs):<br><br>The balance between DAM-like and homeostatic microglia predicts long-term cognitive decline. High DAM levels correlate with vulnerability, while homeostatic microglia appear protective.<br><br>Rare CSF macrophages: Newly identified macrophages in cerebrospinal fluid carry transcriptional signatures strongly linked to AD risk, suggesting immune surveillance in CSF may play a role in disease progression.<br><br>By combining electrophysiology with single-cell genomics, we can start connecting the dots: the neurons that misfire in the presence of amyloid and tau are the same ones exposed to shifts in microglial states. Understanding these interactions opens a new avenue for early detection and intervention.<br><br>The big picture is clear: living human tissue provides a rare opportunity to link molecular changes, cellular behavior, and cognitive outcomes. Our work shows that neuronal firing changes isn\u2019t just a downstream symptom\u2014it\u2019s a measurable, mechanistic effect of early AD pathology, potentially guided by the surrounding immune environment.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p class=\"has-text-align-left\"><\/p>\n\n\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A commentary on how Neurons fire in Early Alzheimer\u2019s: Linking Electrophysiology to Microglial States A few days ago the Alzforum covered again my recent work and its relation to ongoing work in the field of immunology after news emerged following the Alzheimer\u2019s Association International Conference in Toronto My latest work (Dougalis et al., 2025, https:\/\/www.biorxiv.org\/content\/10.1101\/2025.01.07.630516v1.full) [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":2425,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_eb_attr":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-2417","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","entry","has-media"],"_links":{"self":[{"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/posts\/2417","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2417"}],"version-history":[{"count":3,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/posts\/2417\/revisions"}],"predecessor-version":[{"id":2423,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/posts\/2417\/revisions\/2423"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=\/wp\/v2\/media\/2425"}],"wp:attachment":[{"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2417"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2417"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/antoniosdougalis.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2417"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}