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49/100

✓ Peer-reviewed alzhub usefulness score 49 out of 100. Risk genes beyond APOE

Topic: Brain proteins, microglia and lab models

Aging is the principal demographic risk factor for Alzheimer disease (AD), the most common neurodegenerative disorder. Klotho is a key modulator of the aging process and, when overexpressed, extends mammalian lifespan, increases synaptic plasticity, and enhances cognition. Whether klotho can counteract deficits related to neurodegenerative diseases, such as AD, is unknown.

Key findings

Klotho is a key modulator of the aging process and, when overexpressed, extends mammalian lifespan, increases synaptic plasticity, and enhances cognition.
Whether klotho can counteract deficits related to neurodegenerative diseases, such as AD, is unknown.
Here we show that elevating klotho expression decreases premature mortality and network dysfunction in human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD.
Increasing klotho levels prevented depletion of NMDA receptor (NMDAR) subunits in the hippocampus and enhanced spatial learning and memory in hAPP mice.

Why it matters

This study found that increasing klotho expression reduced premature mortality and network dysfunction and prevented depletion of certain cells in hAPP transgenic mice. It is animal research and does not establish that raising klotho treats or prevents Alzheimer's disease in people.

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Study details

Evidence strengthLow

How this study scored 49/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience)
Journal's citation record	4 / 4	Journal of Neuroscience: journal h-index 651 (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	2015 — 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 “transgenic”) — scores zero
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	5 / 7	Cited 197 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	15.2 citations a year over 13 year(s) since 2015
Impact for its field and year	4 / 6	Cited 11.0× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	2 / 6	Cited by 6 other studies in this library
Still being cited	2 / 4	Cited 42 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Lennart Mucke: h-index 108 (OpenAlex, whole career)
Institution's track record	2 / 3	University of California, San Francisco: institution h-index 1,915 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 5 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 25673831)
Free to read	0 / 2	Behind a paywall — scores zero
Total	49 / 100	—

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

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'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

Dubal, D. B., Zhu, L., Sanchez, P. E., Worden, K., Broestl, L., Johnson, E., et al. (2015). Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.5791-12.2015

Vancouver

Dubal DB, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, et al. Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015. doi:10.1523/jneurosci.5791-12.2015. PMID: 25673831.

BibTeX

@article{dubal2015-25673831,
  author  = {Dubal, D. B. and Zhu, L. and Sanchez, P. E. and Worden, K. and Broestl, L. and Johnson, E. and Ho, K. and Yu, G. Q. and others},
  title   = {{Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice}},
  journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year    = {2015},
  doi     = {10.1523/jneurosci.5791-12.2015},
  pmid    = {25673831},
  url     = {https://doi.org/10.1523/jneurosci.5791-12.2015}
}

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