Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease
Voevodskaya O, Sundgren PC, Strandberg O, Zetterberg H, Minthon L, Blennow K, Wahlund LO, Westman E et al.. Neurology, 2016-04-15
Topic: Amyloid, tau and blood-test diagnosis
Objective We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity. Methods In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE. Results Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p Conclusions mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology.
Key findings
- Results Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p Conclusions mI levels are elevated already at asymptomatic stages of AD.
- Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology.
Why it matters
This cross-sectional study found that a brain chemical called myo-inositol was already elevated in cognitively healthy people with abnormal amyloid, and also in healthy APOE ε4 carriers with normal amyloid. This suggests a possible early marker of Alzheimer disease, but it does not show any treatment or prevention.
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Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 87 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.2 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 20 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Tomas P Olsson: h-index 120 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27164711) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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APA 7th
Voevodskaya, O., Sundgren, P. C., Strandberg, O., Zetterberg, H., Minthon, L., Blennow, K., et al. (2016). Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000002672
Vancouver
Voevodskaya O, Sundgren PC, Strandberg O, Zetterberg H, Minthon L, Blennow K, et al. Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease. Neurology. 2016. doi:10.1212/wnl.0000000000002672. PMID: 27164711.
BibTeX
@article{voevodskaya2016-27164711,
author = {Voevodskaya, O. and Sundgren, P. C. and Strandberg, O. and Zetterberg, H. and Minthon, L. and Blennow, K. and Wahlund, L. O. and Westman, E. and others},
title = {{Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease}},
journal = {Neurology},
year = {2016},
doi = {10.1212/wnl.0000000000002672},
pmid = {27164711},
url = {https://doi.org/10.1212/wnl.0000000000002672}
}
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