Golgi fragmentation: One of the earliest organelle phenotypes in Alzheimer's disease neurons
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Golgi fragmentation : One of the earliest organelle phenotypes in Alzheimer's disease neurons. / Haukedal, Henriette; Corsi, Giulia I; Gadekar, Veerendra P; Doncheva, Nadezhda T; Kedia, Shekhar; de Haan, Noortje; Chandrasekaran, Abinaya; Jensen, Pia; Schiønning, Pernille; Vallin, Sarah; Marlet, Frederik Ravnkilde; Poon, Anna; Pires, Carlota; Agha, Fawzi Khoder; Wandall, Hans H; Cirera, Susanna; Simonsen, Anja Hviid; Nielsen, Troels Tolstrup; Nielsen, Jørgen Erik; Hyttel, Poul; Muddashetty, Ravi; Aldana, Blanca I; Gorodkin, Jan; Nair, Deepak; Meyer, Morten; Larsen, Martin Røssel; Freude, Kristine.
In: Frontiers in Neuroscience, Vol. 17, 1120086, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Golgi fragmentation
T2 - One of the earliest organelle phenotypes in Alzheimer's disease neurons
AU - Haukedal, Henriette
AU - Corsi, Giulia I
AU - Gadekar, Veerendra P
AU - Doncheva, Nadezhda T
AU - Kedia, Shekhar
AU - de Haan, Noortje
AU - Chandrasekaran, Abinaya
AU - Jensen, Pia
AU - Schiønning, Pernille
AU - Vallin, Sarah
AU - Marlet, Frederik Ravnkilde
AU - Poon, Anna
AU - Pires, Carlota
AU - Agha, Fawzi Khoder
AU - Wandall, Hans H
AU - Cirera, Susanna
AU - Simonsen, Anja Hviid
AU - Nielsen, Troels Tolstrup
AU - Nielsen, Jørgen Erik
AU - Hyttel, Poul
AU - Muddashetty, Ravi
AU - Aldana, Blanca I
AU - Gorodkin, Jan
AU - Nair, Deepak
AU - Meyer, Morten
AU - Larsen, Martin Røssel
AU - Freude, Kristine
N1 - Copyright © 2023 Haukedal, Corsi, Gadekar, Doncheva, Kedia, de Haan, Chandrasekaran, Jensen, Schiønning, Vallin, Marlet, Poon, Pires, Agha, Wandall, Cirera, Simonsen, Nielsen, Nielsen, Hyttel, Muddashetty, Aldana, Gorodkin, Nair, Meyer, Larsen and Freude.
PY - 2023
Y1 - 2023
N2 - Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model. We recapitulated characteristic late AD phenotypes, such as increased Aβ secretion and Tau hyperphosphorylation, as well as previously well documented mitochondrial and synaptic deficits. Intriguingly, we identified Golgi fragmentation as one of the earliest AD phenotypes, indicating potential impairments in protein processing and post-translational modifications. Computational analysis of RNA sequencing data revealed differentially expressed genes involved in glycosylation and glycan patterns, whilst total glycan profiling revealed minor glycosylation differences. This indicates general robustness of glycosylation besides the observed fragmented morphology. Importantly, we identified that genetic variants in Sortilin-related receptor 1 (SORL1) associated with AD could aggravate the Golgi fragmentation and subsequent glycosylation changes. In summary, we identified Golgi fragmentation as one of the earliest disease phenotypes in AD neurons in various in vivo and in vitro complementary disease models, which can be exacerbated via additional risk variants in SORL1.
AB - Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model. We recapitulated characteristic late AD phenotypes, such as increased Aβ secretion and Tau hyperphosphorylation, as well as previously well documented mitochondrial and synaptic deficits. Intriguingly, we identified Golgi fragmentation as one of the earliest AD phenotypes, indicating potential impairments in protein processing and post-translational modifications. Computational analysis of RNA sequencing data revealed differentially expressed genes involved in glycosylation and glycan patterns, whilst total glycan profiling revealed minor glycosylation differences. This indicates general robustness of glycosylation besides the observed fragmented morphology. Importantly, we identified that genetic variants in Sortilin-related receptor 1 (SORL1) associated with AD could aggravate the Golgi fragmentation and subsequent glycosylation changes. In summary, we identified Golgi fragmentation as one of the earliest disease phenotypes in AD neurons in various in vivo and in vitro complementary disease models, which can be exacerbated via additional risk variants in SORL1.
U2 - 10.3389/fnins.2023.1120086
DO - 10.3389/fnins.2023.1120086
M3 - Journal article
C2 - 36875643
VL - 17
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
M1 - 1120086
ER -
ID: 337997429