{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:51:55Z","timestamp":1782921115207,"version":"3.54.5"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Alzheimer\u2019s disease (AD), the leading cause of major neurocognitive disorder (MNCD) worldwide and in Tunisia, is strongly associated with Apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ). In the present study our aims are to characterize the clinical profile of Tunisian patients, determine\n                      <jats:italic>APOE<\/jats:italic>\n                      allelic and genotypic frequencies, and asses their influence on disease phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included patients with a clinical diagnosis of probable or possible AD, who consulted in the Department of Neurology at Razi University Hospital over a span of 21\u00a0years. Demographic, clinical, and neuropsychological data were assessed.\n                      <jats:italic>APOE<\/jats:italic>\n                      genotyping was performed and its correlation to AD clinical features was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1,010 AD patients, the sex ratio was 0.62, with a mean age at onset of 68.9 \u00b1 9.8\u00a0years. Consanguinity was reported in 30.2% of cases, and a family history of major neurocognitive disorder in 65.3%. The mean Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores were 14.1 \u00b1 7.7 and 6.5 \u00b1 4.8, respectively. Overall, 47.0% of patients carried the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele. The\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b53\/\u03b53 genotype was the most frequent (45.94%), followed by\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b53\/\u03b54 (40.99%). Age at onset was significantly earlier in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers compared to non-carriers (68.17 \u00b1 10.05 vs. 69.53 \u00b1 9.61\u00a0years; p = 0.027). Baseline cognitive performance was also significantly lower in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers, with reduced MMSE (11.65 \u00b1 6.77 vs. 16.40 \u00b1 7.85; p &amp;lt; 0.001) and FAB scores (5.46 \u00b1 4.09 vs. 7.35 \u00b1 5.11; p &amp;lt; 0.001). Neuropsychiatric assessment revealed significant associations between\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriage and visual hallucinations (p = 0.0015), aggressivity (p = 0.0022), disinhibition (p = 0.0039), and aberrant motor behavior (p = 0.0054). Finally, stratified analysis of the AD cohort according to educational attainment and\n                      <jats:italic>APOE<\/jats:italic>\n                      risk allele status demonstrated distinct patterns of cognitive impairment across the different subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele, frequent in North African AD, appears to function not only as a genetic risk factor for AD, but also as a potential indicator, influencing disease onset and clinical severity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1831886","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:25:34Z","timestamp":1782919534000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and neuropsychological profile of Alzheimer\u2019s disease in Tunisia and the impact of APOE gene"],"prefix":"10.3389","volume":"17","author":[{"given":"Alya","family":"Gharbi","sequence":"first","affiliation":[{"name":"Neurology Department, LR18SP03, Razi University Hospital","place":["Tunis, Tunisia"]},{"name":"Faculty of Medicine of Tunis, University of Tunis El Manar","place":["Tunis, Tunisia"]},{"name":"Clinical Investigation Center (CIC) \u201cNeurosciences and Mental Health\u201d, Razi University Hospital","place":["Tunis, Tunisia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikram","family":"Sghaier","sequence":"additional","affiliation":[{"name":"Neurology 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