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36/100

✓ Peer-reviewed alzhub usefulness score 36 out of 100. Treatments

Topic: Disease mechanisms in lab and animal studies

Plain-language summary

Calcium homeostasis plays a major role in maintaining neuronal function under physiological conditions. Amyloid-β (Aβ) initiates pathological processes that include disruption in intracellular calcium levels, so amelioration of the calcium alteration could serve as an indirect functional indicator of treatment efficacy. Therefore, calcium dynamics were used as a measure of functional outcome. We evaluated the effects of the anti-Aβ antibody aducanumab on calcium homeostasis and plaque clearance in aged Tg2576 mice with in vivo multiphoton imaging. Acute topical application of aducanumab to the brain resulted in clearance of amyloid plaques. Although chronic systemic administration of aducanumab in 22-month-old mice did not clear existing plaques, calcium overload was ameliorated over time. Therefore, this antibody likely restores neuronal network function that possibly underlies cognitive deficits, indicating promise as a clinical treatment. In addition, functional readouts such as calcium overload may be a more useful outcome measure to monitor treatment efficacy in models of Alzheimer's disease compared with amyloid burden alone. SIGNIFICANCE STATEMENT Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is currently without a cure. Aducanumab is an anti-amyloid-β antibody being developed for the treatment of AD. Interim analyses of a phase 1b clinical trial have suggested potential beneficial effects on amyloid pathology and cognitive status in patients treated with aducanumab (Sevigny et al., 2016). Here, we show that a murine analog of aducanumab clears amyloid plaques in an acute setting and restores calcium homeostasis disrupted in a mouse model of AD upon chronic treatment. Therefore, we demonstrate that aducanumab reverses a functional outcome measure reflective of neural network activity.

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APA 7th

Kastanenka, K. V., Bussiere, T., Shakerdge, N., Qian, F., Weinreb, P. H., Rhodes, K., et al. (2016). Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.2080-16.2016

Vancouver

Kastanenka KV, Bussiere T, Shakerdge N, Qian F, Weinreb PH, Rhodes K, et al. Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. The Journal of Neuroscience. 2016. doi:10.1523/jneurosci.2080-16.2016.

BibTeX

@article{kastanenka2016-aa97eb96,
  author  = {Kastanenka, Ksenia V. and Bussiere, Thierry and Shakerdge, Naomi and Qian, Fang and Weinreb, Paul H. and Rhodes, Ken and Bacskai, Brian J.},
  title   = {{Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice}},
  journal = {The Journal of Neuroscience},
  year    = {2016},
  doi     = {10.1523/jneurosci.2080-16.2016},
  url     = {https://doi.org/10.1523/jneurosci.2080-16.2016}
}

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.

How to read this study

Design: our record does not state a study design, so check the methods section of the original before weighing the result.
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Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

In addition, functional readouts such as calcium overload may be a more useful outcome measure to monitor treatment efficacy in models of Alzheimer's disease compared with amyloid burden alone.

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Study details

Evidence strengthLow

How this study scored 36/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 20 of the 56 points we could judge it on, which is 36 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (The Journal of Neuroscience)
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	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	Laboratory or animal study (title names “tg2576”) — scores zero
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	— / 7	No citation count (not found in OpenAlex) — left out of this score
Citations per year	— / 5	No citation count or no year — left out of this score
Impact for its field and year	— / 6	No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here	— / 6	Not yet checked against this library's citation graph — left out of this score
Still being cited	— / 4	No yearly citation counts — left out of this score
Senior author's track record	— / 4	Senior author's record not available — left out of this score
Institution's track record	— / 3	No institution listed in OpenAlex — left out of this score
Multicenter collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	1 / 2	Not in PubMed, but has a DOI
Free to read	— / 2	Access not recorded — left out of this score
Points	20 / 56	Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 20 of the 56 points we could judge it on is 36 out of 100.
Total	36 / 100	—

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Where this led: Aducanumab on the treatments page — its current status, approval date, side-effect rate and list price, kept up to date.

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