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Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels
Murray ME, Moloney CM, Kouri N, Syrjanen JA, Matchett BJ, Rothberg DM, Tranovich JF, Sirmans TNH et al.. Molecular neurodegeneration, 2022-12-27
Topic: Amyloid, tau and blood-test diagnosis
Background Advances in ultrasensitive detection of phosphorylated tau (p-tau) in plasma has enabled the use of blood tests to measure Alzheimer's disease (AD) biomarker changes. Examination of postmortem brains of participants with antemortem plasma p-tau levels remains critical to understanding comorbid and AD-specific contribution to these biomarker changes. Methods We analyzed 35 population-based Mayo Clinic Study of Aging participants with plasma p-tau at threonine 181 and threonine 217 (p-tau181, p-tau217) available within 3 years of death. Autopsied participants included cognitively unimpaired, mild cognitive impairment, AD dementia, and non-AD neurodegenerative disorders. Global neuropathologic scales of tau, amyloid-β, TDP-43, and cerebrovascular disease were examined. Regional digital pathology measures of tau (phosphorylated threonine 181 and 217 [pT181, pT217]) and amyloid-β (6F/3D) were quantified in hippocampus and parietal cortex. Neurotransmitter hubs reported to influence development of tangles (nucleus basalis of Meynert) and amyloid-β plaques (locus coeruleus) were evaluated. Results The strongest regional associations were with parietal cortex for tau burden (p-tau181 R = 0.55, p = 0.003; p-tau217 R = 0.66, p 2 = 0.31) and 59% in plasma p-tau217 (Adj. R 2 = 0.59). Neither TDP-43 nor cerebrovascular disease global scales independently contributed to variability. Global scales of tau pathology (β-coefficient = 0.060, p = 0.016) and amyloid-β pathology (β-coefficient = 0.080, p 2 was not associated with plasma p-tau levels, a lower locus coeruleus neuron count/mm 2 was associated with higher plasma p-tau181 (R = -0.50, p = 0.007) and higher plasma p-tau217 (R = -0.55, p = 0.002). Cognitive scores (Adj. R 2 = 0.25-0.32) were predicted by the global tau scale, but not by the global amyloid-β scale or plasma p-tau when modeled simultaneously. Conclusions Higher soluble plasma p-tau levels may be the result of an intersection between insoluble deposits of amyloid-β and tau accumulation in brain, and may be associated with locus coeruleus degeneration.
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APA 7th
Murray, M. E., Moloney, C. M., Kouri, N., Syrjanen, J. A., Matchett, B. J., Rothberg, D. M., et al. (2022). Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels. Molecular neurodegeneration. https://doi.org/10.1186/s13024-022-00578-0
Vancouver
Murray ME, Moloney CM, Kouri N, Syrjanen JA, Matchett BJ, Rothberg DM, et al. Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels. Molecular neurodegeneration. 2022. doi:10.1186/s13024-022-00578-0. PMID: 36575455.
BibTeX
@article{murray2022-36575455,
author = {Murray, M. E. and Moloney, C. M. and Kouri, N. and Syrjanen, J. A. and Matchett, B. J. and Rothberg, D. M. and Tranovich, J. F. and Sirmans, T. N. H. and others},
title = {{Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels}},
journal = {Molecular neurodegeneration},
year = {2022},
doi = {10.1186/s13024-022-00578-0},
pmid = {36575455},
url = {https://doi.org/10.1186/s13024-022-00578-0}
}
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Key findings
- Results The strongest regional associations were with parietal cortex for tau burden (p-tau181 R = 0.55, p = 0.003; p-tau217 R = 0.66, p 2 = 0.31) and 59% in plasma p-tau217 (Adj.
- Global scales of tau pathology (β-coefficient = 0.060, p = 0.016) and amyloid-β pathology (β-coefficient = 0.080, p < 0.001) independently predicted plasma p-tau217 when modeled together with co-pathologies, but only amyloid-β (β-coefficient = 0.33, p = 0.021) significantly predicted plasma p-tau181.
- Conclusions Higher soluble plasma p-tau levels may be the result of an intersection between insoluble deposits of amyloid-β and tau accumulation in brain, and may be associated with locus coeruleus degeneration.
Why it matters
In 35 autopsied participants, higher plasma levels of phosphorylated tau were most strongly linked to tau burden in the parietal cortex, and a lower count of locus coeruleus neurons was linked to higher plasma p-tau. This helps explain what blood p-tau measures but does not test any treatment, cure or prevention.
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Study details
- Participants35
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (OpenAlex, 2026-10-29) |
| 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 | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 35 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 56 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.3 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 6.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Michelle M. Mielke: h-index 112 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36575455) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1186/s13024-022-00578-0
- PubMed: 36575455
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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