ArticleThe EMBO journal1995
Production of intracellular amyloid-containing fragments in hippocampal neurons expressing human amyloid precursor protein and protection against amyloidogenesis by subtle amino acid substitutions in the rodent sequence.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 180 citations in OpenAlex.
- Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CNTN4 modulates neural elongation through interplay with APP.Open biology · 2024Article
- Alcohol Use Disorder and Dementia: A Review.Alcohol research : current reviews · 2024Review
- High-Fat Diets in Animal Models of Alzheimer's Disease: How Can Eating Too Much Fat Increase Alzheimer's Disease Risk?Journal of Alzheimer's disease : JAD · 2024Review
- Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.Aging and disease · 2023Article
- Key Residue for Aggregation of Amyloid-β Peptides.ACS chemical neuroscience · 2022Article
- Impact of increased APP gene dose in Down syndrome and the Dp16 mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Modeling the β-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer's disease.Molecular neurodegeneration · 2020Article
- Alzheimer's disease-related dysregulation of mRNA translation causes key pathological features with ageing.Translational psychiatry · 2020Article
- Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer's Disease.Aging and disease · 2019Review
- Heterochromatic genome instability and neurodegeneration sharing similarities with Alzheimer's disease in old Bmi1+/- mice.Scientific reports · 2019Article
- N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-β(1-16) peptides as arginine specific endopeptidase potentially enhancing risk of Alzheimer's disease.Scientific reports · 2018Article
- Understanding the roles of mutations in the amyloid precursor protein in Alzheimer disease.Molecular psychiatry · 2018Review
- APP mouse models for Alzheimer's disease preclinical studies.The EMBO journal · 2017Review
- Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice.Acta neuropathologica communications · 2017Article
- Common Impact of Chronic Kidney Disease and Brain Microhemorrhages on Cerebral Aβ Pathology in SHRSP.Brain pathology (Zurich, Switzerland) · 2017Article
- Differential transgene expression patterns in Alzheimer mouse models revealed by novel human amyloid precursor protein-specific antibodies.Aging cell · 2016Article
- Familial Alzheimer's disease-associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca2+ entry.Science signaling · 2016Article
- Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice.Trends in neurosciences · 2016Review
- Genetic variants associated with neurodegenerative Alzheimer disease in natural models.Biological research · 2016Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A distinguishing feature of Alzheimer's disease (AD) is the deposition of amyloid plaques in brain parenchyma. These plaques arise by the abnormal accumulation of beta A4, a proteolytic fragment of amyloid precursor protein (APP). Despite the fact that neurons are dramatically affected in the course of the disease, little is known about the neuronal processing of APP. To address this question we have expressed in fully mature, synaptically active rat hippocampal neurons, the neuronal form of human APP (APP695), two mutant forms of human APP associated with AD, and the mouse form of APP (a species known not to develop amyloid plaques). Protein expression was achieved via the Semliki Forest Virus system. Expression of wild type human APP695 resulted in the secretion of beta A4-amyloid peptide and the intracellular accumulation of potential amyloidogenic and non-amyloidogenic fragments. The relative amount of amyloid-containing fragments increased dramatically during expression of the clinical mutants, while it decreased strongly when the mouse form of APP was expressed. 'Humanizing' the rodent APP sequence by introducing three mutations in the beta A4-region also led to increased production of amyloid peptide to levels similar to those obtained with human APP. The single Gly601 to Arg substitution alone was sufficient to triple the ratio of beta A4-peptide to non-amyloidogenic p3-peptide. Due to the capacity of these cells to secrete and accumulate intracellular amyloid fragments, we hypothesize that in the pathogenesis of AD there is a positive feed-back loop where neurons are both producers and victims of amyloid, leading to neuronal degeneration and dementia.(ABSTRACT TRUNCATED AT 250 WORDS)
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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.