In vivo hippocampal subfield shape related to TDP-43, amyloid beta, and tau pathologies

Veronika Hanko, Alexandra C. Apple, Kathryn I. Alpert, Kristen N. Warren, Julie A. Schneider, Konstantinos Arfanakis, David A. Bennett, Lei Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Despite advances in the development of biomarkers for Alzheimer's disease (AD), accurate ante-mortem diagnosis remains challenging because a variety of neuropathologic disease states can coexist and contribute to the AD dementia syndrome. Here, we report a neuroimaging study correlating hippocampal deformity with regional AD and transactive response DNA-binding protein of 43 kDA pathology burden. We used hippocampal shape analysis of ante-mortem T1-weighted structural magnetic resonance imaging images of 42 participants from two longitudinal cohort studies conducted by the Rush Alzheimer's Disease Center. Surfaces were generated for the whole hippocampus and zones approximating the underlying subfields using a previously developed automated image-segmentation pipeline. Multiple linear regression models were constructed to correlate the shape with pathology measures while accounting for covariates, with relationships mapped out onto hippocampal surface locations. A significant relationship existed between higher paired helical filaments–tau burden and inward hippocampal shape deformity in zones approximating CA1 and subiculum which persisted after accounting for coexisting pathologies. No significant patterns of inward surface deformity were associated with amyloid-beta or transactive response DNA-binding protein of 43 kDA after including covariates. Our findings indicate that hippocampal shape deformity measures in surface zones approximating CA1 may represent a biomarker for postmortem AD pathology.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalNeurobiology of Aging
Volume74
DOIs
StatePublished - Feb 2019

Fingerprint

Amyloid
Alzheimer Disease
Pathology
DNA-Binding Proteins
Linear Models
Hippocampus
Biomarkers
Neuroimaging
Longitudinal Studies
Cohort Studies
Magnetic Resonance Imaging

Keywords

  • Alzheimer's disease
  • Biomarker
  • Hippocampus
  • Neuroimaging
  • TDP-43

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Hanko, Veronika ; Apple, Alexandra C. ; Alpert, Kathryn I. ; Warren, Kristen N. ; Schneider, Julie A. ; Arfanakis, Konstantinos ; Bennett, David A. ; Wang, Lei. / In vivo hippocampal subfield shape related to TDP-43, amyloid beta, and tau pathologies. In: Neurobiology of Aging. 2019 ; Vol. 74. pp. 171-181.
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abstract = "Despite advances in the development of biomarkers for Alzheimer's disease (AD), accurate ante-mortem diagnosis remains challenging because a variety of neuropathologic disease states can coexist and contribute to the AD dementia syndrome. Here, we report a neuroimaging study correlating hippocampal deformity with regional AD and transactive response DNA-binding protein of 43 kDA pathology burden. We used hippocampal shape analysis of ante-mortem T1-weighted structural magnetic resonance imaging images of 42 participants from two longitudinal cohort studies conducted by the Rush Alzheimer's Disease Center. Surfaces were generated for the whole hippocampus and zones approximating the underlying subfields using a previously developed automated image-segmentation pipeline. Multiple linear regression models were constructed to correlate the shape with pathology measures while accounting for covariates, with relationships mapped out onto hippocampal surface locations. A significant relationship existed between higher paired helical filaments–tau burden and inward hippocampal shape deformity in zones approximating CA1 and subiculum which persisted after accounting for coexisting pathologies. No significant patterns of inward surface deformity were associated with amyloid-beta or transactive response DNA-binding protein of 43 kDA after including covariates. Our findings indicate that hippocampal shape deformity measures in surface zones approximating CA1 may represent a biomarker for postmortem AD pathology.",
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Hanko, V, Apple, AC, Alpert, KI, Warren, KN, Schneider, JA, Arfanakis, K, Bennett, DA & Wang, L 2019, 'In vivo hippocampal subfield shape related to TDP-43, amyloid beta, and tau pathologies', Neurobiology of Aging, vol. 74, pp. 171-181. https://doi.org/10.1016/j.neurobiolaging.2018.10.013

In vivo hippocampal subfield shape related to TDP-43, amyloid beta, and tau pathologies. / Hanko, Veronika; Apple, Alexandra C.; Alpert, Kathryn I.; Warren, Kristen N.; Schneider, Julie A.; Arfanakis, Konstantinos; Bennett, David A.; Wang, Lei.

In: Neurobiology of Aging, Vol. 74, 02.2019, p. 171-181.

Research output: Contribution to journalArticle

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AU - Arfanakis, Konstantinos

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AU - Wang, Lei

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