Evidence map›Paper›PMID 38594621›Full record

ArticleBMC neurology2024

Onset of Alzheimer disease in apolipoprotein ɛ4 carriers is earlier in butyrylcholinesterase K variant carriers.

Roger M Lane, Taher Darreh-Shori, Candice Junge, Dan Li, Qingqing Yang, Amanda L Edwards, Danielle L Graham, Katrina Moore, Catherine J Mummery

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03186989 (A Randomized, Double-Blind, Placebo-Controlled Study, Followed by an Open-Label Extension, to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 814907 in Patients With Mild Alzheimer's Disease), which is not on this map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03186989 phase1completednot on this map

A Randomized, Double-Blind, Placebo-Controlled Study, Followed by an Open-Label Extension, to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 814907 in Patients With Mild Alzheimer's Disease

TypeinterventionalSponsorIonis Pharmaceuticals, Inc.Ran2017 to 2022Enrolled46ConditionsMild Alzheimer's DiseaseArmsIONIS MAPTRx, Placebo
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Roger M LaneIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, 92010, USA. rlane@ionisph.com.
Taher Darreh-ShoriDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatric, Karolinska Institutet, Stockholm, Sweden.
Candice JungeIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
Dan LiIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
Qingqing YangIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
Amanda L EdwardsBiogen, Cambridge, MA, USA.
Danielle L GrahamBiogen, Cambridge, MA, USA.
Katrina MooreIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
Catherine J MummeryDementia Research Centre, Institute of Neurology, London, UK.
Ionis Pharmaceuticals (United States) · USBiogen (United States) · USKarolinska Institutet · SEUK Dementia Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe authors sought to examine the impact of the K-variant of butyrylcholinesterase (BCHE-K) carrier status on age-at-diagnosis of Alzheimer disease (AD) in APOE4 carriers.

methodsPatients aged 50-74 years with cerebrospinal fluid (CSF) biomarker-confirmed AD, were recruited to clinical trial (NCT03186989 since June 14, 2017). Baseline demographics, disease characteristics, and biomarkers were evaluated in 45 patients according to BCHE-K and APOE4 allelic status in this post-hoc study.

resultsIn APOE4 carriers (N = 33), the mean age-at-diagnosis of AD in BCHE-K carriers (n = 11) was 6.4 years earlier than in BCHE-K noncarriers (n = 22, P < .001, ANOVA). In APOE4 noncarriers (N = 12) there was no observed influence of BCHE-K. APOE4 carriers with BCHE-K also exhibited slightly higher amyloid and tau accumulations compared to BCHE-K noncarriers. A predominantly amyloid, limited tau, and limbic-amnestic phenotype was exemplified by APOE4 homozygotes with BCHE-K. In the overall population, multiple regression analyses demonstrated an association of amyloid accumulation with APOE4 carrier status (P < .029), larger total brain ventricle volume (P < .021), less synaptic injury (Ng, P < .001), and less tau pathophysiology (p-tau

conclusionThese findings have implications for the genetic architecture of prognosis in early AD, not the genetics of susceptibility to AD. In patients with early AD aged less than 75 years, the mean age-at-diagnosis of AD in APOE4 carriers was reduced by over 6 years in BCHE-K carriers versus noncarriers. The functional status of glia may explain many of the effects of APOE4 and BCHE-K on the early AD phenotype.

trial registrationNCT03186989 since June 14, 2017.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4Apolipoproteins EButyrylcholinesteraseChildHumansPhenotypeAmyloid beta-PeptidesApoE protein, humanApolipoprotein E4Apolipoproteins EBCHE protein, humanButyrylcholinesteraseAmyloidApolipoprotein EButyrylcholinesteraseCholinergicGlial activationInnate immuneSex differencesTau

Identifiers

PMID38594621
PMCPMC11003149
OpenAlexW4394615838

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.