Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals
Open accessAbstract
Animal models of Alzheimer's disease have suggested that tau pathology propagation, facilitated by amyloid pathology, may occur along connected pathways. To investigate these ideas in humans, we combined amyloid scans with longitudinal data on white matter connectivity, hippocampal volume, tau positron emission tomography and memory performance in 256 cognitively healthy older individuals. Lower baseline hippocampal volume was associated with increased mean diffusivity of the connecting hippocampal cingulum bundle (HCB). HCB diffusivity predicted tau accumulation in the downstream-connected posterior cingulate cortex in amyloid-positive but not in amyloid-negative individuals. Furthermore, HCB diffusivity predicted memory decline in amyloid-positive individuals with high posterior cingulate cortex tau binding. Our results provide in vivo evidence that higher amyloid pathology strengthens the association between HCB diffusivity and tau accumulation in the downstream posterior cingulate cortex and facilitates memory decline. This confirms amyloid's crucial role in potentiating neural vulnerability and memory decline marking the onset of preclinical Alzheimer's disease.
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A recent longitudinal study in subjects characterized by amyloid and tau PET suggests that fibre tract alterations may be conducive to tau spreading and thus precede grey matter alterations in the projection zones of a tract.
“Interestingly, a recent longitudinal study in subjects characterized by amyloid and tau PET suggests that fibre tract alterations may be conducive to tau spreading and thus precede grey matter alterations in the projection zones of a tract (Jacobs et al., 2018).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Jacobs et al., 2018
The Results (page unavailable) report that baseline hippocampal cingulum diffusivity predicted later tau accumulation in the connected posterior cingulate cortex in amyloid-positive individuals. The Discussion interprets tract changes as potentially related to tau spreading. However, the study did not establish that tract alterations precede grey-matter alterations generally; its downstream measure was tau accumulation, not grey-matter structural change. (LLM, conf=0.86)
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References 74 · Cited by 270
Research works printed but not linked: 1
- [66]Wechsler DS WAIS-III, Wechsler Adult Intelligence Scale—Third Edition, Administration and Scoring Manual The Psychological Corporation New York 1997
- Authors
- Jacobs, H. I. L., Hedden, T., Schultz, A. P., Sepulcre, J., Perea, R. D., Amariglio, R. E., Papp, K. V., Rentz, D. M., Sperling, R. A., & Johnson, K. A.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Jacobs, Heidi I. L.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-02-05
- Volume
- 21
- Issue
- 3
- Pages
- 424-431
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5857215
- OpenAlex
- W2794050431
- Cited by
- 270
- References
- 74
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 30 · 2023: 20 · 2022: 42 · 2021: 39 · 2020: 39 · 2019: 31 · 2018: 24
- FWCI
- 25.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- Biogen
- National Institutes of Health (5u01ag024904-10, 1s10rr019307-01, 1s10od010364-01a1, 7p41eb022544-08, 1s10rr021110-01a1, 1s10rr023043-01)
- National Institute on Aging (U01-AG-024904, K01AG040197, R01AG053509, R01AG026484, R21AG038994, K24AG035007, U01AG010483, R01AG046396, R01AG027435, R01AG037497, P50AG005134, U19AG032438, U01AG032438, K23AG053422, R01AG034556, U19AG024904, P01AG036694)
- National Institute of Biomedical Imaging and Bioengineering (P41-EB022544, K23EB019023, R01EB014894, P41EB015896)
- National Center for Research Resources (S10-RR019307, S10-RR-023043, S10‐RR‐021110, S10RR023401)
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- Alzheimer's disease, amyloid pathology, tau accumulation, white matter connectivity, posterior cingulate cortex, hippocampal volume, mean diffusivity, memory decline, preclinical Alzheimer's disease, tau PET, amyloid PET, older adults
- MeSH terms
- Aged, Female, Gyrus Cinguli, Hippocampus, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory, Memory Disorders, Neural Pathways, Psychomotor Performance, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Healthy Volunteers, White Matter
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