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58/100

✓ Peer-reviewed alzhub usefulness score 58 out of 100. Biomarkers

Topic: Brain proteins, microglia and lab models

Objective To determine whether site-specific tau phosphorylation occupancy (ratio of phosphorylated to unphosphorylated tau) is associated with BDNF Val66Met in presymptomatic and symptomatic DIAD. Results Of 374 study participants, 144 were mutation noncarriers, 156 were presymptomatic mutation carriers, and 74 were symptomatic carriers. In presymptomatic mutation carriers, compared with Val66 homozygotes, Met66 carriers showed significantly poorer episodic memory (d = 0.62; 95% CI, 0.28-0.95), lower hippocampal volume (d = 0.40; 95% CI, 0.09-0.71), and higher p-tau217/tau217 (d = 0.64; 95% CI, 0.30-0.97), p-tau181/tau181 (d = 0.65; 95% CI, 0.32-0.99), and mass spectrometry total tau (d = 0.43; 95% CI, 0.10-0.76). In symptomatic mutation carriers, Met66 carriers showed significantly poorer global cognition (d = 1.17; 95% CI, 0.65-1.66) and higher p-tau217/tau217 (d = 0.53; 95% CI, 0.05-1.01), mass spectrometry total tau (d = 0.78; 95% CI, 0.28-1.25), and p-tau205/tau205 (d = 0.97; 95% CI, 0.46-1.45), when compared with Val66 homozygotes. Conclusions and relevance In DIAD, clinical disease stage and BDNF Met66 were associated with cognitive impairment and levels of site-specific tau phosphorylation. This suggests that pharmacological strategies designed to increase neurotrophic support in the presymptomatic stages of AD may be beneficial.

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APA 7th

Lim, Y. Y., Maruff, P., Barthélemy, N. R., Goate, A., Hassenstab, J., Sato, C., et al. (2022). Association of BDNF Val66Met With Tau Hyperphosphorylation and Cognition in Dominantly Inherited Alzheimer Disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2021.5181

Vancouver

Lim YY, Maruff P, Barthélemy NR, Goate A, Hassenstab J, Sato C, et al. Association of BDNF Val66Met With Tau Hyperphosphorylation and Cognition in Dominantly Inherited Alzheimer Disease. JAMA neurology. 2022. doi:10.1001/jamaneurol.2021.5181. PMID: 35099506.

BibTeX

@article{lim2022-35099506,
  author  = {Lim, Y. Y. and Maruff, P. and Barthélemy, N. R. and Goate, A. and Hassenstab, J. and Sato, C. and Fagan, A. M. and Benzinger, T. L. S. and others},
  title   = {{Association of BDNF Val66Met With Tau Hyperphosphorylation and Cognition in Dominantly Inherited Alzheimer Disease}},
  journal = {JAMA neurology},
  year    = {2022},
  doi     = {10.1001/jamaneurol.2021.5181},
  pmid    = {35099506},
  url     = {https://doi.org/10.1001/jamaneurol.2021.5181}
}

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Key findings

Objective To determine whether site-specific tau phosphorylation occupancy (ratio of phosphorylated to unphosphorylated tau) is associated with BDNF Val66Met in presymptomatic and symptomatic DIAD.
Results Of 374 study participants, 144 were mutation noncarriers, 156 were presymptomatic mutation carriers, and 74 were symptomatic carriers.
In presymptomatic mutation carriers, compared with Val66 homozygotes, Met66 carriers showed significantly poorer episodic memory (d = 0.62; 95% CI, 0.28-0.95), lower hippocampal volume (d = 0.40; 95% CI, 0.09-0.71), and higher p-tau217/tau217 (d = 0.64; 95% CI, 0.30-0.97), p-tau181/tau181 (d = 0.65; 95% CI, 0.32-0.99), and mass spectrometry total tau (d = 0.43; 95% CI, 0.10-0.76).
In symptomatic mutation carriers, Met66 carriers showed significantly poorer global cognition (d = 1.17; 95% CI, 0.65-1.66) and higher p-tau217/tau217 (d = 0.53; 95% CI, 0.05-1.01), mass spectrometry total tau (d = 0.78; 95% CI, 0.28-1.25), and p-tau205/tau205 (d = 0.97; 95% CI, 0.46-1.45), when compared with Val66 homozygotes.
Conclusions and relevance In DIAD, clinical disease stage and BDNF Met66 were associated with cognitive impairment and levels of site-specific tau phosphorylation.

Why it matters

In dominantly inherited Alzheimer's disease, carriers of the BDNF Met66 variant showed poorer memory and cognition and higher levels of phosphorylated tau than Val66 homozygotes, both before and after symptoms appeared. The authors suggest that boosting neurotrophic support in presymptomatic stages might help, but this is a suggestion from an observational cohort study, not evidence that any treatment works.

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Study details

Study designcohort study
Participants527
Evidence strengthModerate

How this study scored 58/100

Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (JAMA neurology)
Journal's citation record	2 / 4	JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29)
Study design	7 / 12	A cohort study following people over time
Strength of evidence	3 / 5	Rated “moderate” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	3 / 5	2022 — within 6 year(s) of the newest study here
Sample size	2 / 4	527 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	3 / 7	Cited 37 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	6.2 citations a year over 6 year(s) since 2022
Impact for its field and year	3 / 6	Cited 4.2× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	2 / 4	Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Lori Smith: h-index 31 (OpenAlex, whole career)
Institution's track record	2 / 3	Washington University in St. Louis: institution h-index 1,962 (OpenAlex)
Multi-centre collaboration	3 / 3	OpenAlex lists 17 institution(s) in 3 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 35099506)
Free to read	0 / 2	Behind a paywall — scores zero
Total	58 / 100	—

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