ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 64 citations in OpenAlex.
- Effect of the Icelandic Mutation APPBiomolecules · 2025Article
- Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Critical thinking of Alzheimer's transgenic mouse model: current research and future perspective.Science China. Life sciences · 2023Review
- A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer's disease mouse model.Nature communications · 2023Article
- Apolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology.Aging brain · 2022Article
- Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives.Frontiers in behavioral neuroscience · 2021Article
- Effect of Treadmill Exercise and Trans-Cinnamaldehyde against d-Galactose- and Aluminum Chloride-Induced Cognitive Dysfunction in Mice.Brain sciences · 2020Article
- Brain region-specific lipid alterations in the PLB4 hBACE1 knock-in mouse model of Alzheimer's disease.Lipids in health and disease · 2020Article
- Knock-in of Mutated hTAU Causes Insulin Resistance, Inflammation and Proteostasis Disturbance in a Mouse Model of Frontotemporal Dementia.Molecular neurobiology · 2020Article
- Evaluating Circadian Dysfunction in Mouse Models of Alzheimer's Disease: Where Do We Stand?Frontiers in neuroscience · 2020Review
- Decay in Retinoic Acid Signaling in Varied Models of Alzheimer's Disease and In-Vitro Test of Novel Retinoic Acid Receptor Ligands (RAR-Ms) to Regulate Protective Genes.Journal of Alzheimer's disease : JAD · 2020Article
- Asiatic Acid Attenuated Aluminum Chloride-Induced Tau Pathology, Oxidative Stress and Apoptosis Via AKT/GSK-3β Signaling Pathway in Wistar Rats.Neurotoxicity research · 2019Article
- Reduced presynaptic vesicle stores mediate cellular and network plasticity defects in an early-stage mouse model of Alzheimer's disease.Molecular neurodegeneration · 2019Article
- The beta secretase BACE1 regulates the expression of insulin receptor in the liver.Nature communications · 2018Article
- Detection of time-, frequency- and direction-resolved communication within brain networks.Scientific reports · 2018Article
- The Implication of the Brain Insulin Receptor in Late Onset Alzheimer's Disease Dementia.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer's disease and track disease progression and cognitive decline.Acta neuropathologica · 2016Article
- Transnasal delivery of human A-beta peptides elicits impaired learning and memory performance in wild type mice.BMC neuroscience · 2016Article
- Neuronal human BACE1 knockin induces systemic diabetes in mice.Diabetologia · 2016Article
- Toward more predictive genetic mouse models of Alzheimer's disease.Brain research bulletin · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Key neuropathological hallmarks of Alzheimer's disease (AD) are elevated levels of amyloid β-peptide (Aβ) species generated via amyloid precursor protein (APP) endoproteolysis and cleavage by the rate-limiting β-site enzyme 1 (BACE1). Because rodents do not develop amyloid pathologies, we here investigated whether AD-like endophenotypes can be created in mice by expression of human bace1. To avoid pitfalls of existing models, we introduced hbace1 via knock-in under the control of the CaMKII α promoter into the safe HPRT locus. We report amyloidogenic processing of murine APP in the hBACE1 mice (termed PLB4), resulting in the formation of toxic APP metabolites that accumulate intra- and extraneuronally in hippocampus and cortex. Pronounced accumulation of Aβ*56 and Aβ hexamers in the absence of plaque deposition was detected in brain tissue from symptomatic PLB4 mice. Heightened levels of inflammation (gliosis) also appeared in several AD-related brain regions (dentate gyrus, hippocampal area CA1, piriform and parietal cortices) at 6 and 12 months of age. Behaviorally, deficits in habituation to a novel environment and semantic-like memory (social transmission of food preference) were detected from 3 to 4 months of age. Impairments in spatial learning strategies in long-term reference (water maze) and working memory (Y-maze) tasks presented at 6 months, and were distinct from reductions in locomotor activity and anxiety. Overall, our data indicate for the first time that targeted, subtle forebrain-specific expression through single gene knock-in of hBACE1 is sufficient to generate AD-relevant cognitive impairments amid corresponding histopathologies, confirming human BACE as the key parameter in amyloid pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.