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This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimaging studies on the amygdala.<\/jats:p>\n                  <jats:p>These studies provide strong support for an early role of the amygdala in Alzheimer\u2019s disease and the utility of imaging biomarkers of the amygdala in detecting early changes and predicting decline in cognitive functions and neuropsychiatric symptoms in early stages. We summarize the animal literature on connectivity of the amygdala, demonstrating that amygdala nuclei that show the earliest and strongest accumulation of neurofibrillary tangle pathology are those that are connected to brain regions that also show early neurofibrillary tangle accumulation. Additionally, we propose an alternative pathway of neurofibrillary tangle spreading within the medial temporal lobe between the amygdala and the anterior hippocampus. The proposed existence of this pathway is strengthened by novel experimental data on human functional connectivity.<\/jats:p>\n                  <jats:p>Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer\u2019s disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer\u2019s disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awad411","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T18:33:53Z","timestamp":1702578833000},"page":"816-829","source":"Crossref","is-referenced-by-count":73,"title":["Amidst an amygdala renaissance in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-8836","authenticated-orcid":false,"given":"Kaitlin M","family":"Stouffer","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University , Baltimore, MD, 21218 , USA"},{"name":"Kavli Neuroscience Discovery Institute, Johns Hopkins University , Baltimore, MD, 21218 , USA"},{"name":"Center for Imaging Science, Johns Hopkins University , Baltimore, MD, 21218 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xenia","family":"Grande","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120, Magdeburg , Germany"},{"name":"Institute for Cognitive Neurology and Dementia Research, Otto-von-Guericke University , 39106, Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-5388","authenticated-orcid":false,"given":"Emrah","family":"D\u00fczel","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120, Magdeburg , Germany"},{"name":"Institute for Cognitive Neurology and Dementia Research, Otto-von-Guericke University , 39106, Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurits","family":"Johansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University , 205 02, Lund , Sweden"},{"name":"Division of Clinical Sciences, Helsingborg, Department of Clinical Sciences Lund, Lund University , 221 84, Lund , Sweden"},{"name":"Department of Psychiatry, Helsingborg Hospital , 252 23, Helsingborg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Creese","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter , EX4 4PY, Exeter , UK"},{"name":"Division of Psychology, Department of Life Sciences, Brunel University London , UB8 3PH, Uxbridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0285-1637","authenticated-orcid":false,"given":"Menno P","family":"Witter","sequence":"additional","affiliation":[{"name":"Kavli Institute for Systems Neuroscience, NTNU Norwegian University of Science and Technology , 7491, Trondheim , Norway"},{"name":"KG. Jebsen Centre for Alzheimer\u2019s Disease, NTNU Norwegian University of Science and Technology , 7491, Trondheim , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University , Baltimore, MD, 21218 , USA"},{"name":"Kavli Neuroscience Discovery Institute, Johns Hopkins University , Baltimore, MD, 21218 , USA"},{"name":"Center for Imaging Science, Johns Hopkins University , Baltimore, MD, 21218 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E M","family":"Wisse","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University , 211 84, Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-1883","authenticated-orcid":false,"given":"David","family":"Berron","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120, Magdeburg , Germany"},{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University , 205 02, Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"2024030122265690800_awad411-B1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological staging of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"key":"2024030122265690800_awad411-B2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","article-title":"Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry","volume":"112","author":"Braak","year":"2006","journal-title":"Acta Neuropathol"},{"key":"2024030122265690800_awad411-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","article-title":"National institute on aging-Alzheimer\u2019s association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease","volume":"8","author":"Hyman","year":"2012","journal-title":"Alzheimers Dement"},{"key":"2024030122265690800_awad411-B4","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.neurobiolaging.2016.09.011","article-title":"Alzheimer\u2019s disease neuroimaging initiative. 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