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Pathological drivers of neurodegeneration in suspected non-Alzheimer’s disease pathophysiology

Wisse, L. E.M. LU orcid ; de Flores, R. ; Xie, L. ; Das, S. R. ; McMillan, C. T. ; Trojanowski, J. Q. ; Grossman, M. LU ; Lee, E. B. ; Irwin, D. and Yushkevich, P. A. , et al. (2021) In Alzheimer's Research and Therapy 13.
Abstract

Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjects. Methods: Subjects with antemortem MRI and autopsy data were selected from ADNI (n=63) and the University of Pennsylvania (n=156). Pathological diagnoses and semi-quantitative scores of MTL tau, neuritic plaques, α-synuclein, and TDP-43 pathology and MTL structural MRI measures from antemortem T1-weighted MRI scans were obtained. β-amyloid... (More)

Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjects. Methods: Subjects with antemortem MRI and autopsy data were selected from ADNI (n=63) and the University of Pennsylvania (n=156). Pathological diagnoses and semi-quantitative scores of MTL tau, neuritic plaques, α-synuclein, and TDP-43 pathology and MTL structural MRI measures from antemortem T1-weighted MRI scans were obtained. β-amyloid status (A+/A−) was determined by CERAD score and neurodegeneration status (N+/N−) by hippocampal volume. Results: SNAP reflects a heterogeneous group of pathological diagnoses. In ADNI, SNAP (A−N+) had significantly more neuropathological diagnoses than A+N+. In the A− group, tau pathology was associated with hippocampal, entorhinal cortex, and Brodmann area 35 volume/thickness and TDP-43 pathology with hippocampal volume. Conclusion: SNAP had a heterogeneous profile with more mixed pathologies than A+N+. Moreover, a role for TDP-43 and tau pathology in driving MTL neurodegeneration in the absence of β-amyloid was supported.

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published
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keywords
Hippocampus, Limbic-predominant age-related TDP-43 encephalopathy, Medial temporal lobe, Neurodegeneration, Neurodegenerative pathologies, Neuropathologies diagnosis, Primary age-related tauopathy, Suspected non-Alzheimer’s pathophysiology
in
Alzheimer's Research and Therapy
volume
13
article number
100
publisher
BioMed Central (BMC)
external identifiers
  • pmid:33990226
  • scopus:85105963749
ISSN
1758-9193
DOI
10.1186/s13195-021-00835-2
language
English
LU publication?
yes
id
8b2e1f8a-17bb-4ae0-bf8e-eacb1089a904
date added to LUP
2021-06-02 15:57:59
date last changed
2025-03-10 17:12:30
@article{8b2e1f8a-17bb-4ae0-bf8e-eacb1089a904,
  abstract     = {{<p>Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjects. Methods: Subjects with antemortem MRI and autopsy data were selected from ADNI (n=63) and the University of Pennsylvania (n=156). Pathological diagnoses and semi-quantitative scores of MTL tau, neuritic plaques, α-synuclein, and TDP-43 pathology and MTL structural MRI measures from antemortem T1-weighted MRI scans were obtained. β-amyloid status (A+/A−) was determined by CERAD score and neurodegeneration status (N+/N−) by hippocampal volume. Results: SNAP reflects a heterogeneous group of pathological diagnoses. In ADNI, SNAP (A−N+) had significantly more neuropathological diagnoses than A+N+. In the A− group, tau pathology was associated with hippocampal, entorhinal cortex, and Brodmann area 35 volume/thickness and TDP-43 pathology with hippocampal volume. Conclusion: SNAP had a heterogeneous profile with more mixed pathologies than A+N+. Moreover, a role for TDP-43 and tau pathology in driving MTL neurodegeneration in the absence of β-amyloid was supported.</p>}},
  author       = {{Wisse, L. E.M. and de Flores, R. and Xie, L. and Das, S. R. and McMillan, C. T. and Trojanowski, J. Q. and Grossman, M. and Lee, E. B. and Irwin, D. and Yushkevich, P. A. and Wolk, D. A.}},
  issn         = {{1758-9193}},
  keywords     = {{Hippocampus; Limbic-predominant age-related TDP-43 encephalopathy; Medial temporal lobe; Neurodegeneration; Neurodegenerative pathologies; Neuropathologies diagnosis; Primary age-related tauopathy; Suspected non-Alzheimer’s pathophysiology}},
  language     = {{eng}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Pathological drivers of neurodegeneration in suspected non-Alzheimer’s disease pathophysiology}},
  url          = {{http://dx.doi.org/10.1186/s13195-021-00835-2}},
  doi          = {{10.1186/s13195-021-00835-2}},
  volume       = {{13}},
  year         = {{2021}},
}