Mitochondrial Dynamics and Bioenergetics in iPSC-Derived Neurons with Familial Alzheimer's Disease Mutations
MacMullen, C. M.; Sharma, N.; Davis, R. L.
Show abstract
Mitochondrial (MT) dysfunction is a hallmark of Alzheimers Disease (AD), but the specific defects across forms of AD are unknown. We measured multiple parameters of MT dynamics and function, and neurite degeneration, in iPSC-derived human neurons possessing natural and engineered mutations in PS1, PS2, and APP genes. Mutations in all three genes altered MT function measured by basal, ATP-linked, and maximal oxygen consumption rate; and spare respiratory capacity, with PS1/PS2 alleles being more severe than APP mutations. Electron flow through Complexes I-IV was decreased in PS1/PS2 mutations but; in contrast, APP alleles had only modest impairments of CI and CII. We measured aspects of MT dynamics including fragmentation, and neurite degeneration, both of which were dramatic in PS1/PS2 alleles, but essentially absent in APP alleles. The marked differences in MT pathology may occur from the distinct ways APP is processed into A{beta} and may correlate with the disease severity.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Ataxia Telangiectasia patient-derived neuronal and brain organoid models reveal mitochondrial dysfunction and oxidative stress 95%
- Regional interneuron transcriptional changes reveal pathologic markers of disease progression in a mouse model of Alzheimer's disease 95%
- Bioenergetic and Protein Processing Imbalances Synergize in iPSC-Dopamine neurons from Individuals with Idiopathic Parkinsons Disease 94%
Similar papers in this journal
- TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus 94%
- Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease 94%
- C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimers disease 94%
Similar papers in this journal
- Tau depletion in human neurons mitigates A beta-driven toxicity 96%
- Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids 95%
- Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease 95%
Similar papers in this journal
- Alpha-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinsons disease 94%
- A Trem2*R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques 93%
- Diabetic phenotype in mouse and humans with β-amyloid pathology reduces the number of microglia around β-amyloid plaques 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.