{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:18:00Z","timestamp":1779099480214,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"This work was supported in part by grants from Neurosurgery First-class Discipline Funding Project of the Second Affiliated Hospital of Harbin Medical University."}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Idiopathic normal pressure hydrocephalus (INPH) is a reversible neurological disorder presenting with cognitive decline, urinary incontinence, and gait disturbance, yet it is often misdiagnosed as Alzheimer's disease (AD) due to overlapping features. Magnetic resonance imaging (MRI) highlights structural differences, but their causal links to disease manifestations remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the causal relationships between brain structures and INPH\/AD through Mendelian randomization (MR) and to explore genetic mechanisms underlying structural variations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 83 brain phenotypes from the UK Biobank and INPH\/AD data from the FinnGen cohort using bidirectional MR. Differentially expressed genes (DEGs) in MR-identified brain regions were obtained from the Allen Human Brain Atlas and examined via bioinformatics analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MR revealed 12 brain structures associated with INPH and 5 with AD, identifying 13 distinct regions differentiating the two disorders across temporal, frontal, occipital, and parietal lobes, as well as the basal ganglia and limbic system. Genetic analyses identified 205 DEGs linked to these regions, enriched in pathways regulating neurodevelopment, neuronal differentiation, and synaptic plasticity. Notably, the neuroactive ligand\u2013receptor interaction pathway was significantly implicated, suggesting a mechanism contributing to cerebrospinal fluid circulation abnormalities in INPH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study integrates MR and bioinformatics to reveal structural and genetic factors distinguishing INPH from AD. These findings provide new insights into the pathogenesis of INPH, improve diagnostic precision, and may inform targeted therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251379046","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T17:46:38Z","timestamp":1758131198000},"page":"671-680","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying differential brain structures and genetic mechanisms between Alzheimer's disease and idiopathic normal pressure hydrocephalus"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5673-1643","authenticated-orcid":false,"given":"Wencai","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000168185.29659.C5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102891"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-90020-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/gps.70060"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4838"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-83874-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlaf010"},{"key":"e_1_3_3_9_2","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies NM","year":"2018","unstructured":"Davies NM, Holmes MV, Davey Smith G. 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