ArticleActa neuropathologica2013
The Alzheimer's β-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques.
Article in Acta neuropathologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 152 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
152 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- The Amyloid-β Pathway in Alzheimer's Disease.Molecular psychiatry · 2021Pooled it
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- Dysregulated oligodendrocyte and myelin dynamics as an early pathological feature of neuropil degeneration in Alzheimer's disease: an ultrastructural study.Acta neuropathologica communications · 2026Article
- Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing.medRxiv : the preprint server for health sciences · 2026Article
- Mitochondrial dysfunction and programmed cell death in Alzheimer's disease: A retrospective bioinformatics study.Medicine · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.bioRxiv : the preprint server for biology · 2026Article
- Design and synthesis of new phosphazine and triazole derivatives for treatment of Alzheimer's disease: modulating ROS/JNK and Wnt/β-catenin signaling pathways.RSC advances · 2026Article
- BACE-1 and ADAM-10 as Potential Peripheral Biomarkers for Alzheimer's Disease.Current pharmaceutical design · 2026Review
- Trofinetide Improves Cognitive Function in APP/PS1 Mice by Suppressing Inflammation and Apoptosis.Molecular neurobiology · 2025Article
- BACE1 Expression Is Required for Proper Synaptic Vesicle Dynamics in the Hippocampus.Journal of neurochemistry · 2025Article
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Regulation of Apoptotic Pathways by MicroRNAs: A Therapeutic Strategy for Alzheimer's Disease.Molecular neurobiology · 2025Review
- Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.Cell stem cell · 2025Article
- The UNC5C T835M mutation associated with Alzheimer's disease leads to neurodegeneration involving oxidative stress and hippocampal atrophy in aged mice.Molecular neurodegeneration · 2025Article
- Annexin A6 membrane repair protein protects against amyloid-induced dystrophic neurites and tau phosphorylation in Alzheimer's disease model mice.Acta neuropathologica · 2025Article
- Alleviation of Neurological Disorders by Targeting Neurodegenerative-Associated Enzymes: Natural and Synthetic Molecules.International journal of molecular sciences · 2025Review
- Long-term systemic androgen deprivation partially modulates neuroinflammation in male AppScientific reports · 2025Article
- Bacopa monnieri phytochemicals as promising BACE1 inhibitors for Alzheimer's disease therapy.Scientific reports · 2025Article
- Comprehensive investigation of multiple targets in the development of newer drugs for the Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Demyelination-derived lysophosphatidylserine promotes microglial dysfunction and neuropathology in a mouse model of Alzheimer's disease.Cellular & molecular immunology · 2025Article
92 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) is the β-secretase that initiates Aβ production in Alzheimer's disease (AD). BACE1 levels are increased in AD, which could contribute to pathogenesis, yet the mechanism of BACE1 elevation is unclear. Furthermore, the normal function of BACE1 is poorly understood. We localized BACE1 in the brain at both the light and electron microscopic levels to gain insight into normal and pathophysiologic roles of BACE1 in health and AD, respectively. Our findings provide the first ultrastructural evidence that BACE1 localizes to vesicles (likely endosomes) in normal hippocampal mossy fiber terminals of both non-transgenic and APP transgenic (5XFAD) mouse brains. In some instances, BACE1-positive vesicles were located near active zones, implying a function for BACE1 at the synapse. In addition, BACE1 accumulated in swollen dystrophic autophagosome-poor presynaptic terminals surrounding amyloid plaques in 5XFAD cortex and hippocampus. Importantly, accumulations of BACE1 and APP co-localized in presynaptic dystrophies, implying increased BACE1 processing of APP in peri-plaque regions. In primary cortical neuron cultures, treatment with the lysosomal protease inhibitor leupeptin caused BACE1 levels to increase; however, exposure of neurons to the autophagy inducer trehalose did not reduce BACE1 levels. This suggests that BACE1 is degraded by lysosomes but not by autophagy. Our results imply that BACE1 elevation in AD could be linked to decreased lysosomal degradation of BACE1 within dystrophic presynaptic terminals. Elevated BACE1 and APP levels in plaque-associated presynaptic dystrophies could increase local peri-plaque Aβ generation and accelerate amyloid plaque growth in AD.
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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.