Home › Research › Brain scans and imaging
Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity
Huijbers W, Schultz AP, Papp KV, LaPoint MR, Hanseeuw B, Chhatwal JP, Hedden T, Johnson KA et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018-11-27
Topic: Plasma and spinal-fluid biomarkers
Animal studies demonstrate that hyperactive neurons facilitate early accumulation and spread of tau and amyloid-β proteins in the pathological cascade of Alzheimer's disease (AD). Human neuroimaging studies have linked hippocampal hyperactivity to amyloid-β accumulation, apolipoprotein ε4 (APOE4) and clinical progression from prodromal AD to clinical dementia. The relationship between hippocampal hyperactivity and early AD molecular pathology (amyloid-β and tau accumulation) before clinical symptoms remains to be elucidated. Here, we studied 120 clinically normal older humans (80 females/40 males) enrolled in the Harvard Aging Brain Study. We measured functional magnetic resonance imaging (fMRI) activity during successful memory encoding and amyloid-β accumulation with PiB-positron emission tomography imaging. Additionally, we measured tau accumulation using AV1451 PET imaging in a subset of 87 participants. In this subset, we found that inferior temporal tau accumulation was associated with increased fMRI activity in the hippocampus, but showed no clear association with amyloid. Together, the findings support a hypothetical model of the evolution of preclinical AD that place hippocampal hyperactivity concurrent with spread of tau pathology to neocortical regions before clinical impairment. SIGNIFICANCE STATEMENT The circumstances under which the hippocampus becomes hyperactive in preclinical stages of Alzheimer's disease (AD) have thus far remained elusive. Recent advances in positron emission tomography (PET) tracers now enable in vivo characterization of amyloid-β and tau accumulation. Here, we combine amyloid and tau PET with functional magnetic resonance imaging (fMRI) to examine the association between Alzheimer's disease pathology and memory-related brain activity in clinically normal older adults. We found an association between increased hippocampal activity and tau accumulation in the inferior temporal cortex. These data suggest that the pathogenesis of hippocampal hyperactivity occurs concurrent with the spread of tau pathology from the entorhinal cortex to the neocortex, before the clinical manifestations of Alzheimer's disease.
Key findings
- In this subset, we found that inferior temporal tau accumulation was associated with increased fMRI activity in the hippocampus, but showed no clear association with amyloid.
- We found an association between increased hippocampal activity and tau accumulation in the inferior temporal cortex.
- These data suggest that the pathogenesis of hippocampal hyperactivity occurs concurrent with the spread of tau pathology from the entorhinal cortex to the neocortex, before the clinical manifestations of Alzheimer's disease.
New to this subject? Start with our plain-English guide: Brain scans & tests →
Study details
- Participants120
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 120 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30482786) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Huijbers, W., Schultz, A. P., Papp, K. V., LaPoint, M. R., Hanseeuw, B., Chhatwal, J. P., et al. (2019). Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.1397-18.2018
Vancouver
Huijbers W, Schultz AP, Papp KV, LaPoint MR, Hanseeuw B, Chhatwal JP, et al. Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2019. doi:10.1523/jneurosci.1397-18.2018. PMID: 30482786.
BibTeX
@article{huijbers2019-30482786,
author = {Huijbers, W. and Schultz, A. P. and Papp, K. V. and LaPoint, M. R. and Hanseeuw, B. and Chhatwal, J. P. and Hedden, T. and Johnson, K. A. and others},
title = {{Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2019},
doi = {10.1523/jneurosci.1397-18.2018},
pmid = {30482786},
url = {https://doi.org/10.1523/jneurosci.1397-18.2018}
}
Related studies in Brain scans and imaging
Also tagged “18f”
319 studies in the library carry the topic tag “18f”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 319 tagged studies.