Dataset Information

Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease.

ABSTRACT:

Background

Alzheimer's disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A[Formula: see text]) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact.

Methods

We use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A[Formula: see text] and tau on the excitation-inhibition balance of the local nodes.

Results

We found a clear dominance of A[Formula: see text] over tau in the early disease stages (MCI), while tau dominates over A[Formula: see text] in the latest stages (AD). We identify crucial roles for A[Formula: see text] and tau in complex neuronal dynamics and demonstrate the viability of using regional distributions to define models of large-scale brain function in AD.

Conclusions

Our study provides further insight into the dynamics and complex interplay between these two proteins, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.

SUBMITTER: Patow G

PROVIDER: S-EPMC10696890 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease.

Patow Gustavo G Stefanovski Leon L Ritter Petra P Deco Gustavo G Kobeleva Xenia X

Alzheimer's research & therapy 20231205 1

<h4>Background</h4>Alzheimer's disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A[Formula: see text]) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact.<h4>Methods</h4>We use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A[Formula: see text] and tau on the excitation-inhibition balance of the local nodes.<h4>Results</h4 ...[more]

PMID: 38053164

Similar Datasets

Project description:Alzheimer's disease is a neurodegenerative disease that accounts for most of the 50-million dementia cases worldwide in 2018. A large amount of evidence supports the amyloid cascade hypothesis, which states that amyloid-beta accumulation triggers tau hyperphosphorylation and aggregation in form of neurofibrillary tangles, and these aggregates lead to inflammation, synaptic impairment, neuronal loss, and thus to cognitive decline and behavioral abnormalities. The poor correlation found between cognitive decline and amyloid plaques, have led the scientific community to question whether amyloid-beta accumulation is actually triggering neurodegeneration in Alzheimer's disease. The occurrence of tau neurofibrillary tangles better correlates to neuronal loss and clinical symptoms and, although amyloid-beta may initiate the cascade of events, tau impairment is likely the effector molecule of neurodegeneration. Recently, it has been shown that amyloid-beta and tau cooperatively work to impair transcription of genes involved in synaptic function and, more importantly, that downregulation of tau partially reverses transcriptional perturbations. Despite mounting evidence points to an interplay between amyloid-beta and tau, some factors could independently affect both pathologies. Thus, the dual pathway hypothesis, which states that there are common upstream triggers causing both amyloid-beta and tau abnormalities has been proposed. Among others, the immune system seems to be strongly involved in amyloid-beta and tau pathologies. Other factors, as the apolipoprotein E ε4 isoform has been suggested to act as a link between amyloid-beta and tau hyperphosphorylation. Interestingly, amyloid-beta-immunotherapy reduces not only amyloid-beta but also tau levels in animal models and in clinical trials. Likewise, it has been shown that tau-immunotherapy also reduces amyloid-beta levels. Thus, even though amyloid-beta immunotherapy is more advanced than tau-immunotherapy, combined amyloid-beta and tau-directed therapies at early stages of the disease have recently been proposed as a strategy to stop the progression of Alzheimer's disease.

Dataset Information

Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease.

Background

Methods

Results

Conclusions

Publications

Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease.

Similar Datasets

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