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Amidst an amygdala renaissance in Alzheimer's disease

Stouffer, Kaitlin M ; Grande, Xenia ; Duezel, Emrah ; Johansson, Maurits LU ; Creese, Byron ; Witter, Menno P ; Miller, Michael I ; Wisse, Laura E M LU orcid and Berron, David LU (2023) In Brain : a journal of neurology
Abstract

The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal Braak & Braak article (1991). 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. These studies provide strong support for an early role of the amygdala in Alzheimer's 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... (More)

The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal Braak & Braak article (1991). 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. These studies provide strong support for an early role of the amygdala in Alzheimer's 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. Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer's disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer's disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer's disease.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Alzheimer’s disease, amygdala, tau pathology, neuropsychiatric symptoms, clinical imaging biomarkers, medial temporal lobe connectivity
in
Brain : a journal of neurology
pages
14 pages
publisher
Oxford University Press
external identifiers
  • scopus:85186087151
  • pmid:38109776
ISSN
1460-2156
DOI
10.1093/brain/awad411
language
English
LU publication?
yes
id
2d2b152f-1215-4753-a8e7-b703bfb950cf
date added to LUP
2024-02-28 14:39:04
date last changed
2024-04-17 09:45:08
@article{2d2b152f-1215-4753-a8e7-b703bfb950cf,
  abstract     = {{<p>The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal Braak &amp; Braak article (1991). 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. These studies provide strong support for an early role of the amygdala in Alzheimer's 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. Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer's disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer's disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer's disease.</p>}},
  author       = {{Stouffer, Kaitlin M and Grande, Xenia and Duezel, Emrah and Johansson, Maurits and Creese, Byron and Witter, Menno P and Miller, Michael I and Wisse, Laura E M and Berron, David}},
  issn         = {{1460-2156}},
  keywords     = {{Alzheimer’s disease; amygdala; tau pathology; neuropsychiatric symptoms; clinical imaging biomarkers; medial temporal lobe connectivity}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain : a journal of neurology}},
  title        = {{Amidst an amygdala renaissance in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1093/brain/awad411}},
  doi          = {{10.1093/brain/awad411}},
  year         = {{2023}},
}