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Upregulated function of mitochondria-associated ER membranes in Alzheimer disease
Area-Gomez E, Del Carmen Lara Castillo M, Tambini MD, Guardia-Laguarta C, de Groof AJ, Madra M, Ikenouchi J, Umeda M et al.. The EMBO journal, 2012-08-14
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD) is associated with aberrant processing of the amyloid precursor protein (APP) by γ-secretase, via an unknown mechanism. We recently showed that presenilin-1 and -2, the catalytic components of γ-secretase, and γ-secretase activity itself, are highly enriched in a subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAMs). We now show that MAM function and ER-mitochondrial communication-as measured by cholesteryl ester and phospholipid synthesis, respectively-are increased significantly in presenilin-mutant cells and in fibroblasts from patients with both the familial and sporadic forms of AD.
Key findings
- We recently showed that presenilin-1 and -2, the catalytic components of γ-secretase, and γ-secretase activity itself, are highly enriched in a subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAMs).
- We now show that MAM function and ER-mitochondrial communication-as measured by cholesteryl ester and phospholipid synthesis, respectively-are increased significantly in presenilin-mutant cells and in fibroblasts from patients with both the familial and sporadic forms of AD.
- We also show that MAM is an intracellular detergent-resistant lipid raft (LR)-like domain, consistent with the known presence of presenilins and γ-secretase activity in rafts.
- These findings may help explain not only the aberrant APP processing but also a number of other biochemical features of AD, including altered lipid metabolism and calcium homeostasis.
Why it matters
This study found that mitochondria-associated ER membrane function and ER-mitochondrial communication are increased in cells with presenilin mutations and in fibroblasts from patients with familial and sporadic Alzheimer's disease. These were cell-based experiments, so it is not yet known whether targeting these membranes could treat or prevent Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 56/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The EMBO journal) |
| Journal's citation record | 4 / 4 | The EMBO Journal: journal h-index 563 (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 | 1 / 5 | 2012 — 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 | 6 / 7 | Cited 641 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 40.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 5 / 6 | Cited 21.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 140 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Eric A. Schon: h-index 95 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22892566) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Area-Gomez, E., Del Carmen Lara Castillo, M., Tambini, M. D., Guardia-Laguarta, C., de Groof, A. J., Madra, M., et al. (2012). Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. The EMBO journal. https://doi.org/10.1038/emboj.2012.202
Vancouver
Area-Gomez E, Del Carmen Lara Castillo M, Tambini MD, Guardia-Laguarta C, de Groof AJ, Madra M, et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. The EMBO journal. 2012. doi:10.1038/emboj.2012.202. PMID: 22892566.
BibTeX
@article{areagomez2012-22892566,
author = {Area-Gomez, E. and Del Carmen Lara Castillo, M. and Tambini, M. D. and Guardia-Laguarta, C. and de Groof, A. J. and Madra, M. and Ikenouchi, J. and Umeda, M. and others},
title = {{Upregulated function of mitochondria-associated ER membranes in Alzheimer disease}},
journal = {The EMBO journal},
year = {2012},
doi = {10.1038/emboj.2012.202},
pmid = {22892566},
url = {https://doi.org/10.1038/emboj.2012.202}
}
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