Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease

Christine L. Tardif, Gabriel A. Devenyi, Robert S.C. Amaral, Sandra Pelleieux, Judes Poirier, Pedro Rosa-Neto, John C.S. Breitner, M. Mallar Chakravarty

Research output: Contribution to journalArticle

Abstract

Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) e4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

Original languageEnglish (US)
JournalHuman Brain Mapping
DOIs
StateAccepted/In press - Jan 1 2017
Externally publishedYes

Fingerprint

Cerebrospinal Fluid
Alzheimer Disease
Biomarkers
Hippocampus
Amyloid
Apolipoprotein E4
Spinal Puncture
Amyloid Plaques
Neuroimaging
Atrophy
Alleles
Magnetic Resonance Imaging
Pathology
White Matter

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • APOE e4
  • Cerebrospinal fluid biomarkers
  • Fimbria
  • Fornix
  • Hippocampal subfields
  • Preclinical
  • Structural magnetic resonance imaging
  • Tau

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology

Cite this

Tardif, C. L., Devenyi, G. A., Amaral, R. S. C., Pelleieux, S., Poirier, J., Rosa-Neto, P., ... Chakravarty, M. M. (Accepted/In press). Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease. Human Brain Mapping. https://doi.org/10.1002/hbm.23897

Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease. / Tardif, Christine L.; Devenyi, Gabriel A.; Amaral, Robert S.C.; Pelleieux, Sandra; Poirier, Judes; Rosa-Neto, Pedro; Breitner, John C.S.; Chakravarty, M. Mallar.

In: Human Brain Mapping, 01.01.2017.

Research output: Contribution to journalArticle

Tardif, Christine L. ; Devenyi, Gabriel A. ; Amaral, Robert S.C. ; Pelleieux, Sandra ; Poirier, Judes ; Rosa-Neto, Pedro ; Breitner, John C.S. ; Chakravarty, M. Mallar. / Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease. In: Human Brain Mapping. 2017.
@article{13fa1c2818b5485a9e4044a0c2efebb0,
title = "Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease",
abstract = "Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) e4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.",
keywords = "Alzheimer's disease, Amyloid-β, APOE e4, Cerebrospinal fluid biomarkers, Fimbria, Fornix, Hippocampal subfields, Preclinical, Structural magnetic resonance imaging, Tau",
author = "Tardif, {Christine L.} and Devenyi, {Gabriel A.} and Amaral, {Robert S.C.} and Sandra Pelleieux and Judes Poirier and Pedro Rosa-Neto and Breitner, {John C.S.} and Chakravarty, {M. Mallar}",
year = "2017",
month = "1",
day = "1",
doi = "10.1002/hbm.23897",
language = "English (US)",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease

AU - Tardif, Christine L.

AU - Devenyi, Gabriel A.

AU - Amaral, Robert S.C.

AU - Pelleieux, Sandra

AU - Poirier, Judes

AU - Rosa-Neto, Pedro

AU - Breitner, John C.S.

AU - Chakravarty, M. Mallar

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) e4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

AB - Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) e4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

KW - Alzheimer's disease

KW - Amyloid-β

KW - APOE e4

KW - Cerebrospinal fluid biomarkers

KW - Fimbria

KW - Fornix

KW - Hippocampal subfields

KW - Preclinical

KW - Structural magnetic resonance imaging

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=85034789814&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034789814&partnerID=8YFLogxK

U2 - 10.1002/hbm.23897

DO - 10.1002/hbm.23897

M3 - Article

C2 - 29164798

AN - SCOPUS:85034789814

JO - Human Brain Mapping

JF - Human Brain Mapping

SN - 1065-9471

ER -