期刊
HUMAN BRAIN MAPPING
卷 39, 期 2, 页码 971-984出版社
WILEY
DOI: 10.1002/hbm.23897
关键词
Alzheimer's disease; amyloid-beta; APOE epsilon 4; cerebrospinal fluid biomarkers; fimbria; fornix; hippocampal subfields; preclinical; structural magnetic resonance imaging; tau
资金
- McGill University
- Fonds de Research du Quebec - Sante
- Douglas Hospital Research Centre and Foundation
- Government of Canada
- Canadian Foundation for Innovation
- Levesque Foundation
- Pfizer Canada
- Development Office of the McGill University Faculty of Medicine
- Douglas Hospital Research Centre Foundation
- Canada foundation for innovation under Compute Canada
- Government of Ontario
- Ontario Research Fund - Research Excellence
- University of Toronto
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-beta 1-42 (A beta) 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) epsilon 4 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 A beta. Individuals with a reduction in CSF A beta 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 A beta. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF A beta. 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.
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