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71/100

✓ Peer-reviewed alzhub usefulness score 71 out of 100. Genetics

Topic: Brain proteins, microglia and lab models

Plain-language summary

Importance The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neuropathology in a sex-specific manner. Objective To evaluate sex differences in the association between APOE and markers of AD neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy. Design, setting, and participants This multicohort study selected data from 10 longitudinal cohort studies of normal aging and AD. Cohorts had variable recruitment criteria and follow-up intervals and included population-based and clinic-based samples. Inclusion in our analysis required APOE genotype data and either CSF data available for analysis. Analyses began on November 6, 2017, and were completed on December 20, 2017. Main outcomes and measures Biomarker analyses included levels of β-amyloid 42, total tau, and phosphorylated tau measured in CSF. Autopsy analyses included Consortium to Establish a Registry for Alzheimer's Disease staging for neuritic plaques and Braak staging for neurofibrillary tangles. Results Of the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years. Of the 5109 patients in the autopsy cohort, 2813 were women, 4953 were white, and the mean (SD) age was 84 (9) years. After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β = 0.41; 95% CI, 0.27-0.55; P Conclusions and relevance We provide robust evidence of a stronger association between APOE-ε4 and CSF tau levels among women compared with men across multiple independent data sets. Interestingly, APOE-ε4 is not differentially associated with autopsy measures of neurofibrillary tangles. Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.

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APA 7th

Hohman, T. J., Dumitrescu, L., Barnes, L. L., Thambisetty, M., Beecham, G., Kunkle, B., et al. (2018). Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA neurology. https://doi.org/10.1001/jamaneurol.2018.0821

Vancouver

Hohman TJ, Dumitrescu L, Barnes LL, Thambisetty M, Beecham G, Kunkle B, et al. Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA neurology. 2018. doi:10.1001/jamaneurol.2018.0821. PMID: 29801024.

BibTeX

@article{hohman2018-29801024,
  author  = {Hohman, T. J. and Dumitrescu, L. and Barnes, L. L. and Thambisetty, M. and Beecham, G. and Kunkle, B. and Gifford, K. A. and Bush, W. S. and others},
  title   = {{Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau}},
  journal = {JAMA neurology},
  year    = {2018},
  doi     = {10.1001/jamaneurol.2018.0821},
  pmid    = {29801024},
  url     = {https://doi.org/10.1001/jamaneurol.2018.0821}
}

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How to read this study

Design: this is a follow-up (cohort) study. People are observed over time and not assigned to anything, so an association can reflect other differences between groups. Look at how long follow-up lasted, how many dropped out, and whether the authors adjusted for age, education and other health conditions.
Size: the record lists 1,798 participants. Ask whether that is enough for the question, and who they were.
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 moderate. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Moderate means the abstract mentions a cohort, case-control or longitudinal design. 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

Importance The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men.
Results Of the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years.
After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β = 0.41; 95% CI, 0.27-0.55; P < .001) and phosphorylated tau (β = 0.24; 95% CI, 0.09-0.38; P = .001), whereby APOE showed a stronger association among women compared with men.
Interestingly, APOE-ε4 is not differentially associated with autopsy measures of neurofibrillary tangles.
Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.

Why it matters

Pooling data from 10 cohort studies (1,798 people with spinal-fluid tests, mostly white, average age 70), the authors found that the APOE-ε4 gene variant was more strongly linked to spinal-fluid tau levels in women than in men. In a separate group of 5,109 people examined after death, ε4 was "not differentially associated" with tau tangles in the brain, so the sex difference appeared in fluid tau measured during life but not in tangles seen at autopsy. This is an observational association. It does not predict an individual's risk or point to any treatment.

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Study details

Study designcohort study
Participants1,798
Evidence strengthModerate

How this study scored 71/100

Published in a leading specialty journal, and it is a cohort study following 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 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	2 / 5	2018 — within 10 year(s) of the newest study here
Sample size	3 / 4	1,798 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	6 / 7	Cited 339 times (OpenAlex, 2026-10-10)
Citations per year	4 / 5	33.9 citations a year over 10 year(s) since 2018
Impact for its field and year	4 / 6	Cited 19.1× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	4 / 6	Cited by 35 other studies in this library
Still being cited	3 / 4	Cited 110 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Angela Lee Jefferson: h-index 60 (OpenAlex, whole career)
Institution's track record	3 / 3	University of Washington: institution h-index 3,540 (OpenAlex)
Multicenter collaboration	3 / 3	OpenAlex lists 25 institution(s) in 3 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 29801024)
Free to read	0 / 2	Behind a paywall — scores zero
Total	71 / 100	—

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