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Insulin Resistance is Associated with Higher Cerebrospinal Fluid Tau Levels in Asymptomatic APOEɛ4 Carriers
Starks EJ, Patrick O'Grady J, Hoscheidt SM, Racine AM, Carlsson CM, Zetterberg H, Blennow K, Okonkwo OC et al.. Journal of Alzheimer's disease : JAD, 2015-01-01
Topic: Plasma and spinal-fluid biomarkers
Background Insulin resistance (IR) is linked with the occurrence of pathological features observed in Alzheimer's disease (AD), including neurofibrillary tangles and amyloid plaques. However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear. Objective To determine the extent to which IR is linked with amyloid and tau pathology in late-middle-age. Method Cerebrospinal fluid (CSF) samples collected from 113 participants enrolled in the Wisconsin Registry for Alzheimer's Prevention study (mean age = 60.6 years), were assayed for AD-related markers of interest: Aβ₄₂, P-Tau181, and T-Tau. IR was determined using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Linear regression was used to test the effect of IR, and APOEɛ4, on tau and amyloid pathology. We hypothesized that greater IR would be associated with higher CSF P-Tau181 and T-Tau, and lower CSF Aβ₄₂. Results No significant main effects of HOMA-IR on P-Tau181, T-Tau, or Aβ₄₂ were observed; however, significant interactions were observed between HOMA-IR and APOEɛ4 on CSF markers related to tau. Among APOEɛ4 carriers, higher HOMA-IR was associated with higher P-Tau181 and T-Tau. Among APOEɛ4 non-carriers, HOMA-IR was negatively associated with P-Tau181 and T-Tau. We found no effects of IR on Aβ₄₂ levels in CSF. Conclusion IR among asymptomatic APOEɛ4 carriers was associated with higher P-Tau181 and T-Tau in late-middle age. The results suggest that IR may contribute to tau-related neurodegeneration in preclinical AD. The findings may have implications for developing prevention strategies aimed at modifying IR in mid-life.
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APA 7th
Starks, E. J., Patrick O'Grady, J., Hoscheidt, S. M., Racine, A. M., Carlsson, C. M., Zetterberg, H., et al. (2015). Insulin Resistance is Associated with Higher Cerebrospinal Fluid Tau Levels in Asymptomatic APOEɛ4 Carriers. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-150072
Vancouver
Starks EJ, Patrick O'Grady J, Hoscheidt SM, Racine AM, Carlsson CM, Zetterberg H, et al. Insulin Resistance is Associated with Higher Cerebrospinal Fluid Tau Levels in Asymptomatic APOEɛ4 Carriers. Journal of Alzheimer's disease : JAD. 2015. doi:10.3233/jad-150072. PMID: 25812851.
BibTeX
@article{starks2015-25812851,
author = {Starks, E. J. and Patrick O'Grady, J. and Hoscheidt, S. M. and Racine, A. M. and Carlsson, C. M. and Zetterberg, H. and Blennow, K. and Okonkwo, O. C. and others},
title = {{Insulin Resistance is Associated with Higher Cerebrospinal Fluid Tau Levels in Asymptomatic APOEɛ4 Carriers}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2015},
doi = {10.3233/jad-150072},
pmid = {25812851},
url = {https://doi.org/10.3233/jad-150072}
}
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Key findings
- However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear.
- We hypothesized that greater IR would be associated with higher CSF P-Tau181 and T-Tau, and lower CSF Aβ₄₂.
- Results No significant main effects of HOMA-IR on P-Tau181, T-Tau, or Aβ₄₂ were observed; however, significant interactions were observed between HOMA-IR and APOEɛ4 on CSF markers related to tau.
- Among APOEɛ4 carriers, higher HOMA-IR was associated with higher P-Tau181 and T-Tau.
- Among APOEɛ4 non-carriers, HOMA-IR was negatively associated with P-Tau181 and T-Tau.
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Study details
- Participants113
- Evidence strengthLow
How this study scored 45/100
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 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| 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 | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 113 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 25812851) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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