ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Partial loss of presenilin impairs age-dependent neuronal survival in the cerebral cortex.
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 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways.Acta neuropathologica communications · 2026Article
- Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.Nature communications · 2024Article
- Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease PSEN1 Δ440 mutation.Human molecular genetics · 2024Article
- Cortical neurodegeneration caused byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Presenilin Deficiency Results in Cellular Cholesterol Accumulation by Impairment of Protein Glycosylation and NPC1 Function.International journal of molecular sciences · 2024Article
- New precision medicine avenues to the prevention of Alzheimer's disease from insights into the structure and function of γ-secretases.The EMBO journal · 2024Review
- Presenilin-1 in smooth muscle cells facilitates hypermuscularization in elastin aortopathy.iScience · 2024Article
- Impaired Skeletal Development by Disruption of Presenilin-1 in Pigs and Generation of Novel Pig Models for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- A familial Alzheimer's disease associated mutation in presenilin-1 mediates amyloid-beta independent cell specific neurodegeneration.PloS one · 2024Article
- Human Presenilin-1 delivered by AAV9 rescues impaired γ-secretase activity, memory deficits, and neurodegeneration inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Selective ferroptosis vulnerability due to familial Alzheimer's disease presenilin mutations.Cell death and differentiation · 2022Article
- Motor Impairments and Dopaminergic Defects Caused by Loss of Leucine-Rich Repeat Kinase Function in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- TM2D genes regulate Notch signaling and neuronal function in Drosophila.PLoS genetics · 2021Article
- Loss of presenilin function enhances tau phosphorylation and aggregation in mice.Acta neuropathologica communications · 2021Article
- Protocols for assessing neurodegenerative phenotypes in Alzheimer's mouse models.STAR protocols · 2021Article
- Article
- Cell-autonomous role of Presenilin in age-dependent survival of cortical interneurons.Molecular neurodegeneration · 2020Article
- Knock-in rats with homozygousThe Journal of biological chemistry · 2020Article
- Novel presenilin 1 and 2 double knock-out cell line for in vitro validation of PSEN1 and PSEN2 mutations.Neurobiology of disease · 2020Article
- Identification and Clinical Analysis of the First Nonsense Mutation in theFrontiers in neurology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the presenilin (PSEN1 and PSEN2) genes are linked to familial Alzheimer's disease (AD) and cause loss of its essential function. Complete inactivation of presenilins in excitatory neurons of the adult mouse cerebral cortex results in progressive memory impairment and age-dependent neurodegeneration, recapitulating key features of AD. In this study, we examine the effects of varying presenilin dosage on cortical neuron survival by generating presenilin-1 conditional knock-out (PS1 cKO) mice carrying two, one, or zero copies of the PS2 gene. We found that PS1 cKO;PS2(+/-) mice at 16 months exhibit marked neurodegeneration in the cerebral cortex with ∼17% reduction of cortical volume and neuron number, as well as astrogliosis and microgliosis compared with ∼50% reduction of cortical volume and neuron number in PS1 cKO;PS2(-/-) mice. Moreover, there are more apoptotic neurons labeled by activated caspase-3 immunoreactivity and TUNEL assay in PS1 cKO;PS2(+/-) mice at 16 months, whereas apoptotic neurons are increased in the PS1 cKO;PS2(-/-) cerebral cortex at 4 months. The accumulation of the C-terminal fragments of the amyloid precursor protein is inversely correlated with PS dosage. Interestingly, levels of PS2 are higher in the cerebral cortex of PS1 cKO mice, suggesting a compensatory upregulation that may provide protection against neurodegeneration in these mice. Together, our findings show that partial to complete loss of presenilin activity causes progressively more severe neurodegeneration in the mouse cerebral cortex during aging, suggesting that impaired presenilin function by PSEN mutations may lead to neurodegeneration and dementia in AD.
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