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Subthreshold Amyloid Predicts Tau Deposition in Aging
Leal SL, Lockhart SN, Maass A, Bell RK, Jagust WJ.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018-04-23
Topic: Plasma and spinal-fluid biomarkers
Current approaches to the early detection of Alzheimer's disease (AD) rely upon classifying individuals as "positive" or "negative" for biomarkers related to the core pathology of β-amyloid (Aβ). However, the accumulation of Aβ begins slowly, years before biomarkers become abnormal. We used longitudinal [ 11 C] Pittsburgh Compound B PET scanning and neuropsychological assessment to investigate the earliest changes in AD pathology and how it affects memory in cognitively normal older humans ( N = 71; mean age 75 years; 35% male). We used [ 18 F] AV-1451 PET scanning at the end of the observation period to measure subsequent tau deposition in a subset of our sample ( N = 37). We found evidence for an inverted-U relationship between baseline Aβ levels and Aβ slope in asymptomatic older adults, suggesting a slowing of Aβ accumulation even in cognitively normal adults. In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of Aβ predicted early tau deposition in cortical Braak regions associated with AD. Amyloid measures were only sensitive to memory decline as baseline levels of Aβ increased, suggesting that pathological accumulation occurs before impacting memory. These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative. SIGNIFICANCE STATEMENT The progressive nature of Alzheimer's disease (AD) necessitates the earliest possible detection of pathological or cognitive change if disease progression is to be slowed. We examined cognitively normal older adults in whom AD pathology is starting to develop, with the goal of early detection of AD pathology or cognitive changes. We found amyloid measures to be sensitive early on in predicting subsequent early tau deposition. Further, it appears that rates of amyloid accumulation already begin to slow in preclinical AD, suggesting that it is a relatively late stage of AD progression. Thus, it is crucial to examine older adults early, before amyloid levels have saturated, to intervene to slow disease progression.
Key findings
- We found evidence for an inverted-U relationship between baseline Aβ levels and Aβ slope in asymptomatic older adults, suggesting a slowing of Aβ accumulation even in cognitively normal adults.
- In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of Aβ predicted early tau deposition in cortical Braak regions associated with AD.
- Amyloid measures were only sensitive to memory decline as baseline levels of Aβ increased, suggesting that pathological accumulation occurs before impacting memory.
- These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative.
- We found amyloid measures to be sensitive early on in predicting subsequent early tau deposition.
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Study details
- Study designlongitudinal study
- Participants71
- Evidence strengthModerate
How this study scored 60/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for 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 35 of the 58 points we could judge it on, which is 60 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 | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 71 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 29686045) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Leal, S. L., Lockhart, S. N., Maass, A., Bell, R. K., & Jagust, W. J. (2018). Subthreshold Amyloid Predicts Tau Deposition in Aging. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.0485-18.2018
Vancouver
Leal SL, Lockhart SN, Maass A, Bell RK, Jagust WJ. Subthreshold Amyloid Predicts Tau Deposition in Aging. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2018. doi:10.1523/jneurosci.0485-18.2018. PMID: 29686045.
BibTeX
@article{leal2018-29686045,
author = {Leal, S. L. and Lockhart, S. N. and Maass, A. and Bell, R. K. and Jagust, W. J.},
title = {{Subthreshold Amyloid Predicts Tau Deposition in Aging}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2018},
doi = {10.1523/jneurosci.0485-18.2018},
pmid = {29686045},
url = {https://doi.org/10.1523/jneurosci.0485-18.2018}
}
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