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45/100

✓ Peer-reviewed alzhub usefulness score 45 out of 100. Treatments

Topic: Brain proteins, microglia and lab models

A recent randomized trial demonstrated clear cerebrospinal-fluid DHA target engagement without detectable improvement in cognition or brain volume over 24 months. A positive result would support a stress-specific mitochondrial execution gate; a negative result would reassign the mechanism to general vulnerability, serial mitochondrial mediation, lipid dominance, or mixed limitation. This result does not prove that DHA lacks biological effects, nor does it establish why functional benefit was not observed. Early biochemical work showed that ACSL6 preferentially promotes DHA internalization, activation to DHA-CoA, and accumulation in differentiating neuronal cells [2]. In induced pluripotent stem cell (iPSC)-derived cortical neurons, changes in the overall membrane PUFA state and in the relative DHA/arachidonic acid (AA) composition altered neuronal activity, morphology, and amyloid-beta production [4]. Together, these findings justify an experimentally defined ACSL6-low membrane prestate in which DHA-rich phospholipids are reduced and AA-containing phospholipid substrate pools are relatively enriched. Human and disease-relevant observations further support mitochondrial abnormalities in AD: patient-derived neurons show altered respiration, redox state and Ca2+ handling [10,11], cortical AD biopsy material shows fewer and more damaged synaptic mitochondria associated with presynaptic vesicle abnormalities [12], and synaptic mitochondrial bioenergetic inefficiency has been linked to Aβ accumulation in aging and amnestic mild cognitive impairment [9].

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Bouchelit, M. E. A. (2026). Stress-Specific Mitochondrial Reserve as a Candidate Modifier of Lipid-Driven Synaptic Failure in Alzheimer Disease. Zenodo (CERN European Organization for Nuclear Research). https://doi.org/10.5281/zenodo.21854145

Vancouver

Bouchelit MEA. Stress-Specific Mitochondrial Reserve as a Candidate Modifier of Lipid-Driven Synaptic Failure in Alzheimer Disease. Zenodo (CERN European Organization for Nuclear Research). 2026. doi:10.5281/zenodo.21854145.

BibTeX

@article{bouchelit2026-371ff4d0,
  author  = {Bouchelit, Mohammed El Amin},
  title   = {{Stress-Specific Mitochondrial Reserve as a Candidate Modifier of Lipid-Driven Synaptic Failure in Alzheimer Disease}},
  journal = {Zenodo (CERN European Organization for Nuclear Research)},
  year    = {2026},
  doi     = {10.5281/zenodo.21854145},
  url     = {https://doi.org/10.5281/zenodo.21854145}
}

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Key findings

A recent randomized trial demonstrated clear cerebrospinal-fluid DHA target engagement without detectable improvement in cognition or brain volume over 24 months.
A positive result would support a stress-specific mitochondrial execution gate; a negative result would reassign the mechanism to general vulnerability, serial mitochondrial mediation, lipid dominance, or mixed limitation.
This result does not prove that DHA lacks biological effects, nor does it establish why functional benefit was not observed.
Early biochemical work showed that ACSL6 preferentially promotes DHA internalization, activation to DHA-CoA, and accumulation in differentiating neuronal cells [2].
In induced pluripotent stem cell (iPSC)-derived cortical neurons, changes in the overall membrane PUFA state and in the relative DHA/arachidonic acid (AA) composition altered neuronal activity, morphology, and amyloid-beta production [4].

Why it matters

A recent randomized trial found clear target engagement of DHA in cerebrospinal fluid but no detectable improvement in cognition or brain volume over 24 months. The authors stress this does not prove DHA lacks biological effects and does not explain why no functional benefit was seen, and they propose mitochondrial reserve as a possible modifier to be tested.

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Study details

Study designrandomized controlled trial
Evidence strengthHigh

How this study scored 45/100

Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on journal's citation record and institution's track record, so those were left out: it earned 42 of the 93 points we could judge it on, which is 45 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Zenodo (CERN European Organization for Nuclear Research))
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
Study design	11 / 12	A randomised controlled trial
Strength of evidence	5 / 5	Rated “high” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	5 / 5	2026 — within 1 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	1 / 2	Randomised (as stated in the record)
Times cited	0 / 7	Cited 0 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.0 citations a year over 2 year(s) since 2026
Impact for its field and year	0 / 6	Cited 0.0× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	0 / 4	Last-listed author Mohammed El Amin Bouchelit: h-index 0 (OpenAlex, whole career)
Institution's track record	— / 3	No institution listed in OpenAlex — left out of this score
Multi-centre collaboration	0 / 3	OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete)
Indexed in PubMed	1 / 2	Not in PubMed, but has a DOI
Free to read	2 / 2	Free to read
Points	42 / 93	Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 42 of the 93 points we could judge it on is 45 out of 100.
Total	45 / 100	—

What each of these 20 components measures, and what this score is not →

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