{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T06:47:43Z","timestamp":1782542863133,"version":"3.54.5"},"reference-count":75,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The locus coeruleus (LC) is an early site of Alzheimer's disease (AD) pathology, yet the role of brainstem astrocytes in early, sex\u2010dependent vulnerability remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In 2\u2010 to 3\u2010month\u2010old APP\/PS1 mice, we combined in vivo proton magnetic resonance spectroscopy (MRS) of the brainstem with region\u2010resolved molecular analyses, including quantitative real\u2010time polymerase chain reaction, amyloid beta 42 (A\u03b242) oligomers enzyme\u2010linked immunosorbent assay, lactate assay, immunohistochemistry, immunoblotting, astrocyte isolation, and 3D structural assessment. Environmental enrichment (EE) served as a non\u2010pharmacologic intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Females exhibited higher brainstem A\u03b242 oligomers and an astrocyte\u2010weighted MRS profile. Pontine glial fibrillary acidic protein (GFAP), complement component 3, and nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells were selectively upregulated without pan\u2010reactive astrocytic and microglial markers. LC\u2010restricted GFAP elevation occurred without changes in astrocyte counts or morphology, indicating a \u201cprimed\u201d state. Females also showed higher lactate levels, increased monocarboxylate transporter 2 expression, and elevations in selected oxidative phosphorylation\u2010associated transcripts, and reduced astrocytic alpha 2A\u2010adrenergic receptor expression. EE normalized noradrenergic and pontine astrocytic changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Female\u2010biased, LC\u2010centric astrocytic priming emerges early in this amyloid\u2010driven model and is modifiable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71168","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T09:34:33Z","timestamp":1770370473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Female\u2010biased astrocytic priming shapes early locus coeruleus vulnerability in an A\u03b2 oligomer milieu"],"prefix":"10.1002","volume":"22","author":[{"given":"Srishti","family":"Kushwaha","sequence":"first","affiliation":[{"name":"Centre for Brain Research Indian Institute of Science  Bangalore India"},{"name":"Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupsa","family":"Roy Choudhury","sequence":"additional","affiliation":[{"name":"Centre for Brain Research Indian Institute of Science  Bangalore India"},{"name":"Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of NMR All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Senthil","family":"Kumaran","sequence":"additional","affiliation":[{"name":"Department of NMR All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smitha","family":"Karunakaran","sequence":"additional","affiliation":[{"name":"Centre for Brain Research Indian Institute of Science  Bangalore 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