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Mitochondria-associated ER membranes in Alzheimer disease
Schon EA, Area-Gomez E.. Molecular and cellular neurosciences, 2012-08-24
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD) is associated with the accumulation in the brain of extracellular neuritic plaques composed mainly of β-amyloid (Aβ) and of intracellular neurofibrillary tangles composed of hyperphosphorylated forms of the microtubule-associated protein tau. It is also associated with other features that have received less attention, including aberrant phospholipid, cholesterol, and calcium metabolism, and altered mitochondrial function and dynamics. The underlying mechanism(s) that might explain these observations are currently unknown. We recently showed that presenilin-1 (PS1), presenilin-2 (PS2), and γ-secretase activity, which processes the amyloid precursor protein (APP) to generate Aβ, are located predominantly in a specialized subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAM). MAM is an intracellular lipid raft-like structure intimately involved in cholesterol and phospholipid lipid metabolism, in calcium homeostasis, and in mitochondrial function and dynamics. The coincidence of the functions associated with MAM with the symptomatology of AD led us to speculate that presenilins play a role in maintaining MAM function. We found that, consistent with this supposition, both MAM function and ER-mitochondrial connectivity are increased significantly in AD, which may help explain many of the biochemical and morphological features of the disease. Based on these findings, we propose that AD is fundamentally a disorder of ER-mitochondrial communication (the "MAM hypothesis"). This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.
Key findings
- Alzheimer disease (AD) is associated with the accumulation in the brain of extracellular neuritic plaques composed mainly of β-amyloid (Aβ) and of intracellular neurofibrillary tangles composed of hyperphosphorylated forms of the microtubule-associated protein tau.
- It is also associated with other features that have received less attention, including aberrant phospholipid, cholesterol, and calcium metabolism, and altered mitochondrial function and dynamics.
- We recently showed that presenilin-1 (PS1), presenilin-2 (PS2), and γ-secretase activity, which processes the amyloid precursor protein (APP) to generate Aβ, are located predominantly in a specialized subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAM).
- The coincidence of the functions associated with MAM with the symptomatology of AD led us to speculate that presenilins play a role in maintaining MAM function.
- We found that, consistent with this supposition, both MAM function and ER-mitochondrial connectivity are increased significantly in AD, which may help explain many of the biochemical and morphological features of the disease.
Why it matters
This work links Alzheimer disease to increased function and connectivity between the endoplasmic reticulum and mitochondria, alongside the known amyloid plaques and tau tangles. It is a speculative mechanism based on prior cell findings, not a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 41 of the 96 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and cellular neurosciences) |
| 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 | 2013 — 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 | 5 / 7 | Cited 265 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.7 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Estela Área-Gómez: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22922446) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 41 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 41 of the 96 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.mcn.2012.07.011
- PubMed: 22922446
- Original source →
- Free full text: Molecular and Cellular Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Schon, E. A., & Area-Gomez, E. (2013). Mitochondria-associated ER membranes in Alzheimer disease. Molecular and cellular neurosciences. https://doi.org/10.1016/j.mcn.2012.07.011
Vancouver
Schon EA, Area-Gomez E. Mitochondria-associated ER membranes in Alzheimer disease. Molecular and cellular neurosciences. 2013. doi:10.1016/j.mcn.2012.07.011. PMID: 22922446.
BibTeX
@article{schon2013-22922446,
author = {Schon, E. A. and Area-Gomez, E.},
title = {{Mitochondria-associated ER membranes in Alzheimer disease}},
journal = {Molecular and cellular neurosciences},
year = {2013},
doi = {10.1016/j.mcn.2012.07.011},
pmid = {22922446},
url = {https://doi.org/10.1016/j.mcn.2012.07.011}
}
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