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Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease
Grosso Jasutkar H, Wasserlein EM, Ishola A, Litt N, Staniszewski A, Arancio O, Yamamoto A.. Autophagy, 2024-07-01
Topic: Amyloid, tau and blood-test diagnosis
Isolated forebrain synaptosomes, rather than total homogenates, from atg7 iKO mice demonstrated accumulation of synaptic proteins, suggesting that the synapse might be a vulnerable site for protein homeostasis disruption. In the symptomatic APP PSEN1 double-transgenic mouse model of AD, we found that the impairment in autophagosome maturation coupled with diminished presence of discrete synaptic proteins in autophagosomes isolated from these mice, leading to the accumulation of one of these proteins in the detergent insoluble protein fraction. Taken together, we conclude that synaptic autophagy plays a role in maintaining protein homeostasis, and that while decreasing autophagy interrupts normal cognitive function, the preservation of locomotion suggests that not all circuits are affected similarly. Our data suggest that the disruption of autophagic activity in AD may have relevance for the cognitive impairment in this adult-onset neurodegenerative disease.
Key findings
- Isolated forebrain synaptosomes, rather than total homogenates, from atg7 iKO mice demonstrated accumulation of synaptic proteins, suggesting that the synapse might be a vulnerable site for protein homeostasis disruption.
- In the symptomatic APP PSEN1 double-transgenic mouse model of AD, we found that the impairment in autophagosome maturation coupled with diminished presence of discrete synaptic proteins in autophagosomes isolated from these mice, leading to the accumulation of one of these proteins in the detergent insoluble protein fraction.
- Taken together, we conclude that synaptic autophagy plays a role in maintaining protein homeostasis, and that while decreasing autophagy interrupts normal cognitive function, the preservation of locomotion suggests that not all circuits are affected similarly.
- Our data suggest that the disruption of autophagic activity in AD may have relevance for the cognitive impairment in this adult-onset neurodegenerative disease.
Why it matters
In mice, turning off autophagy in adulthood disrupted synapse protein balance and caused cognitive impairment, and autophagy problems were also seen in a mouse model of Alzheimer's disease. This is animal research, so it suggests a possible mechanism but does not establish a treatment or cure for people.
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Study details
- Effect sizeor 6.5
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, 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 (Autophagy) |
| Journal's citation record | 2 / 4 | Autophagy: journal h-index 240 (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 | 4 / 5 | 2024 — within 3 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 5.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ai Yamamoto: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38949671) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 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).
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Grosso Jasutkar, H., Wasserlein, E. M., Ishola, A., Litt, N., Staniszewski, A., Arancio, O., et al. (2024). Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease. Autophagy. https://doi.org/10.1080/15548627.2024.2368335
Vancouver
Grosso Jasutkar H, Wasserlein EM, Ishola A, Litt N, Staniszewski A, Arancio O, et al. Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease. Autophagy. 2024. doi:10.1080/15548627.2024.2368335. PMID: 38949671.
BibTeX
@article{grossojasutkar2024-38949671,
author = {Grosso Jasutkar, H. and Wasserlein, E. M. and Ishola, A. and Litt, N. and Staniszewski, A. and Arancio, O. and Yamamoto, A.},
title = {{Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease}},
journal = {Autophagy},
year = {2024},
doi = {10.1080/15548627.2024.2368335},
pmid = {38949671},
url = {https://doi.org/10.1080/15548627.2024.2368335}
}
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