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65/100

✓ Peer-reviewed alzhub usefulness score 65 out of 100. Mild cognitive impairment

Topic: Brain proteins, microglia and lab models

Importance Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. Objective To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). Design, setting, and participants Longitudinal study of consecutive patients who underwent 2 lumbar punctures between the beginning of 1995 and the end of 2010 within the memory clinic-based Amsterdam Dementia Cohort. The study included 163 patients: 37 cognitively normal participants (mean [SE] age, 64 [2] years; 38% female; and mean [SE] Mini-Mental State Examination [MMSE] score, 28 [0.3]), 61 patients with mild cognitive impairment (MCI) (mean [SE] age, 68 [1] years; 38% female; and mean [SE] MMSE score, 27 [0.3]), and 65 patients with AD (mean [SE] age, 65 [1] years; 45% female; and mean [SE] MMSE score, 22 [0.7]). The mean (SE) interval between lumbar punctures was 2.0 (0.1) years, and the mean (SE) duration of cognitive follow-up was 3.8 (0.2) years. Measurements of CSF NGRN levels were obtained in January and February 2014. Main outcome and measure Levels of NGRN in CSF samples. Results Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651-3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04). Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P Conclusions and relevance Neurogranin is a promising biomarker for AD because levels were elevated in patients with AD compared with cognitively normal participants and predicted progression from MCI to AD. Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss.

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APA 7th

Kester, M. I., Teunissen, C. E., Crimmins, D. L., Herries, E. M., Ladenson, J. H., Scheltens, P., et al. (2015). Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2015.1867

Vancouver

Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P, et al. Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease. JAMA neurology. 2015. doi:10.1001/jamaneurol.2015.1867. PMID: 26366630.

BibTeX

@article{kester2015-26366630,
  author  = {Kester, M. I. and Teunissen, C. E. and Crimmins, D. L. and Herries, E. M. and Ladenson, J. H. and Scheltens, P. and van der Flier, W. M. and Morris, J. C. and others},
  title   = {{Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease}},
  journal = {JAMA neurology},
  year    = {2015},
  doi     = {10.1001/jamaneurol.2015.1867},
  pmid    = {26366630},
  url     = {https://doi.org/10.1001/jamaneurol.2015.1867}
}

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Key findings

Results Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651-3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04).
Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P < .001), but not with Aβ42.
Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss.

Why it matters

In 163 memory-clinic patients from the Amsterdam Dementia Cohort who each had two spinal-fluid samples about two years apart, levels of neurogranin, a proposed marker of synapse loss, were higher in Alzheimer's disease than in cognitively normal people (median 2381 vs 1712 pg/mL, P = .04) and tracked closely with tau. Over time, neurogranin rose within cognitively normal participants but not in people with later-stage MCI or Alzheimer's, which the authors say "suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss." The authors call it "a promising biomarker", but the group ranges overlapped, and this study tested diagnosis and monitoring, not a treatment.

Study details

Study designlongitudinal study
Participants163
Evidence strengthModerate

How this study scored 65/100

Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomized / 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 longitudinal study following the same 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	1 / 5	2015 — within 20 year(s) of the newest study here
Sample size	2 / 4	163 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)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	5 / 7	Cited 245 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	18.8 citations a year over 13 year(s) since 2015
Impact for its field and year	4 / 6	Cited 18.6× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	4 / 6	Cited by 30 other studies in this library
Still being cited	3 / 4	Cited 52 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Anne M. Fagan: h-index 122 (OpenAlex, whole career)
Institution's track record	2 / 3	Washington University in St. Louis: institution h-index 1,962 (OpenAlex)
Multicenter collaboration	1 / 3	OpenAlex lists 3 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 26366630)
Free to read	0 / 2	Behind a paywall — scores zero
Total	65 / 100	—

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