Evidence map›Paper›PMID 25621019›Full record

ArticleAlzheimer's research & therapy2014

BACE1 inhibitor drugs in clinical trials for Alzheimer's disease.

Robert Vassar

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

Article in Alzheimer's research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06639282 (SIPO1-AD), which is not on this map. Cited by 181 papers.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed
23.4field-weighted citation impact, top 1% 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.

NCT06639282 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease

TypeinterventionalSponsorSt. Joseph's Hospital and Medical Center, PhoenixRan2025 to 2029Enrolled105ConditionsAlzheimer Disease, Mild Alzheimer Disease, MCI With Increased Risk for Alzheimer Disease, Cognitive Impairment, MildArmsSiponimod, Placebo
3 · Its place in the literature

Who cites it

181 citing papers in PubMed, 411 citations in OpenAlex.

  1. Trial
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  5. The evolving landscape of amyloid-targeting therapies in Alzheimer's disease: progress and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
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  16. A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  17. Article
  18. Review
  19. Review
  20. Article

121 more citing papers are in PubMed but not listed here.

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

1 author at 1 institution in 1 country.

Robert VassarDepartment of Cell and Molecular Biology, Northwestern University, The Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611 USA.
Northwestern University · US

Funding

BACE1 as a Therapeutic Target for Alzheimer's DiseaseR01AG022560 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 2003 to 2017
$4.6M
Molecular Neuropathology and Mechanisms of BACE1 Elevation in Alzheimer's DiseaseR01AG030142 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 2007 to 2019
$3.1M
BACE1 as a Therapeutic Target for Alzheimer's DiseaseRF1AG022560 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 2019 to 2019
$2.0M
NIA NIH HHS R01 AG022560NIA NIH HHS R01 AG030142NIA NIH HHS RF1 AG022560
6 · The paper itself

Abstract

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the β-secretase enzyme required for the production of the neurotoxic β-amyloid (Aβ) peptide that is widely considered to have a crucial early role in the etiology of Alzheimer's disease (AD). As a result, BACE1 has emerged as a prime drug target for reducing the levels of Aβ in the AD brain, and the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. It has proven difficult for the pharmaceutical industry to design BACE1 inhibitor drugs that pass the blood-brain barrier, however this challenge has recently been met and BACE1 inhibitors are now in human clinical trials to test for safety and efficacy in AD patients and individuals with pre-symptomatic AD. Initial results suggest that some of these BACE1 inhibitor drugs are well tolerated, although others have dropped out because of toxicity and it is still too early to know whether any will be effective for the prevention or treatment of AD. Additionally, based on newly identified BACE1 substrates and phenotypes of mice that lack BACE1, concerns have emerged about potential mechanism-based side effects of BACE1 inhibitor drugs with chronic administration. It is hoped that a therapeutic window can be achieved that balances safety and efficacy. This review summarizes the current state of progress in the development of BACE1 inhibitor drugs and the evaluation of their therapeutic potential for AD.

Identifiers

PMID25621019
PMCPMC4304279
OpenAlexW2166109990

What OpenQuestion holds

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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 OpenQuestion graph.