@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) ɛ4 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 = "APOE ɛ4, Alzheimer's disease, amyloid-β, cerebrospinal fluid biomarkers, fimbria, fornix, hippocampal subfields, preclinical, structural magnetic resonance imaging, tau",
author = "{for the PREVENT-AD Research Group} and Tardif, {Christine L.} and Devenyi, {Gabriel A.} and Amaral, {Robert S.C.} and Sandra Pelleieux and Judes Poirier and Pedro Rosa-Neto and John Breitner and Chakravarty, {M. Mallar}",
note = "Funding Information: Data collection and sharing for this project were provided by the PREVENT-AD program. In addition, the authors would like to thank Holly Newbold-Fox for MRI acquisition, Anne Labont{\'e} and Doris Dea for their technical assistance in genotyping and CSF assays, C{\'e}cile Madjar and Jennifer Tremblay-Mercier for study and data coordination. The authors would also like to thank Melissa Appleby, Galina Pogossova, Laura Mahar, Karen Wan, Tanya Lee, Marie-{\'E}lyse Lafaille-Magnan, Justin Kat, David Fontaine and Jason Brandt for the cognitive testing and scoring. A complete list of acknowledgements can be found at: https://preventad.loris.ca/acknowledgements/acknowledgements.php?date52017-06-14. Data collection and sharing for this project was supported by the PREVENT-AD program sponsors: McGill University, the Fonds de Research du Qu{\'e}bec– Sant{\'e}, the Douglas Hospital Research Centre and Foundation, the Government of Canada, the Canadian Foundation for Innovation, the Levesque Foundation, and an unrestricted gift from Pfizer Canada. Private sector contributions are facilitated by the Development Office of the McGill University Faculty of Medicine and by the Douglas Hospital Research Centre Foundation (http://www.douglas.qc.ca/). Hippocampal subfield segmentation was performed on the gpc supercomputer at the SciNet HPC Consortium (https://www.scinethpc.ca). SciNet is funded by: the Canada foundation for innovation under the auspices of compute Canada; the Government of Ontario; Ontario Research Fund - Research Excellence; and the University of Toronto. Funding Information: McGill University; the Fonds de Research du Qu{\'e}bec – Sant{\'e}; the Douglas Hospital Research Centre and Foundation; the Government of Canada; the Canadian Foundation for Innovation; the Levesque Foundation; Pfizer Canada; Development Office of the McGill University Faculty of Medicine and by the Douglas Hospital Research Centre Foundation; Canada foundation for innovation under the auspices of Compute Canada; the Government of Ontario; Ontario Research Fund - Research Excellence; and the University of Toronto. Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",
year = "2018",
month = feb,
doi = "10.1002/hbm.23897",
language = "English (US)",
volume = "39",
pages = "971--984",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",
number = "2",
}