Compensating for synaptic loss in Alzheimer’s disease: A neural modelling study

Kamal Abuhassan; Damien Coyle; Liam Maguire

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with progressive dementia. The clinical symptoms of AD are cognitive and intellectual deficits and behavior dysfunction. EEG has been utilized for diagnosing dementias. There is a strong correlation between cognitive deficit and the degree of the EEG abnormality. EEG spectral analysis in AD patients has shown a decrease in the mean frequency, alpha (8–12 Hz) and beta (13–30 Hz) band powers with a parallel increase in delta (1–3 Hz) and theta (4–7 Hz) band powers compared with those of healthy elderly subjects (Dauwels, Vialatte, & Cichocki, 2011). The EEG abnormalities in AD indicate functional and anatomical impairment of the cerebral cortex affected by the disease. The neuropathology of AD is characterized by an enormous neuronal and synaptic loss in the cerebral cortex and certain subcortical regions, and the formation of pathological proteins (Serrano-Pozo, Frosch, Masliah, & Hyman, 2011). The degree of synaptic loss is the factor most correlated with the severity of AD and cognitive decline (Shankar & Walsh, 2009; Terry et al., 1991). Several experimental studies have found that the neurodegenerative process is accompanied by synaptic compensation mechanisms, “a homeostatic mechanism which maintains the excitatory response of individual neurons and prevents the catastrophic amnesia associated with synapse loss” (Small, 2004; Turrigiano, 2011, 2012). On an activity level, synaptic compensation senses and regulates the firing rate of the network at the neuron or network level (Fröhlich, Bazhenov, & Sejnowski, 2008). Understanding neural activity and compensation mechanisms is a challenge given the limitation in current neuroimaging modalities and imaging brain activity at a microscopic level. Here we investigate the interplay between various synaptic degeneration and compensation mechanisms, and abnormal cortical oscillations based on a large-scale neural model. Results from the models are consistent with a range of human and animal model findings.

Original language	English
Number of pages	1
Publication status	Published - 1 Jan 2013
Event	5th Annual Translational Medicine Conference - Duration: 1 Jan 2013 → …

Conference

Conference	5th Annual Translational Medicine Conference
Period	1/01/13 → …

Bibliographical note

The 5th Annual Translational Medicine Conference ; Conference date: 01-01-2013

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This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

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title = "Compensating for synaptic loss in Alzheimer{\textquoteright}s disease: A neural modelling study",

abstract = "Alzheimer{\textquoteright}s disease (AD) is the most common neurodegenerative disorder associated with progressive dementia. The clinical symptoms of AD are cognitive and intellectual deficits and behavior dysfunction. EEG has been utilized for diagnosing dementias. There is a strong correlation between cognitive deficit and the degree of the EEG abnormality. EEG spectral analysis in AD patients has shown a decrease in the mean frequency, alpha (8–12 Hz) and beta (13–30 Hz) band powers with a parallel increase in delta (1–3 Hz) and theta (4–7 Hz) band powers compared with those of healthy elderly subjects (Dauwels, Vialatte, & Cichocki, 2011). The EEG abnormalities in AD indicate functional and anatomical impairment of the cerebral cortex affected by the disease. The neuropathology of AD is characterized by an enormous neuronal and synaptic loss in the cerebral cortex and certain subcortical regions, and the formation of pathological proteins (Serrano-Pozo, Frosch, Masliah, & Hyman, 2011). The degree of synaptic loss is the factor most correlated with the severity of AD and cognitive decline (Shankar & Walsh, 2009; Terry et al., 1991). Several experimental studies have found that the neurodegenerative process is accompanied by synaptic compensation mechanisms, “a homeostatic mechanism which maintains the excitatory response of individual neurons and prevents the catastrophic amnesia associated with synapse loss” (Small, 2004; Turrigiano, 2011, 2012). On an activity level, synaptic compensation senses and regulates the firing rate of the network at the neuron or network level (Fr{\"o}hlich, Bazhenov, & Sejnowski, 2008). Understanding neural activity and compensation mechanisms is a challenge given the limitation in current neuroimaging modalities and imaging brain activity at a microscopic level. Here we investigate the interplay between various synaptic degeneration and compensation mechanisms, and abnormal cortical oscillations based on a large-scale neural model. Results from the models are consistent with a range of human and animal model findings.",

author = "Kamal Abuhassan and Damien Coyle and Liam Maguire",

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AU - Abuhassan, Kamal

AU - Coyle, Damien

AU - Maguire, Liam

N1 - The 5th Annual Translational Medicine Conference ; Conference date: 01-01-2013

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with progressive dementia. The clinical symptoms of AD are cognitive and intellectual deficits and behavior dysfunction. EEG has been utilized for diagnosing dementias. There is a strong correlation between cognitive deficit and the degree of the EEG abnormality. EEG spectral analysis in AD patients has shown a decrease in the mean frequency, alpha (8–12 Hz) and beta (13–30 Hz) band powers with a parallel increase in delta (1–3 Hz) and theta (4–7 Hz) band powers compared with those of healthy elderly subjects (Dauwels, Vialatte, & Cichocki, 2011). The EEG abnormalities in AD indicate functional and anatomical impairment of the cerebral cortex affected by the disease. The neuropathology of AD is characterized by an enormous neuronal and synaptic loss in the cerebral cortex and certain subcortical regions, and the formation of pathological proteins (Serrano-Pozo, Frosch, Masliah, & Hyman, 2011). The degree of synaptic loss is the factor most correlated with the severity of AD and cognitive decline (Shankar & Walsh, 2009; Terry et al., 1991). Several experimental studies have found that the neurodegenerative process is accompanied by synaptic compensation mechanisms, “a homeostatic mechanism which maintains the excitatory response of individual neurons and prevents the catastrophic amnesia associated with synapse loss” (Small, 2004; Turrigiano, 2011, 2012). On an activity level, synaptic compensation senses and regulates the firing rate of the network at the neuron or network level (Fröhlich, Bazhenov, & Sejnowski, 2008). Understanding neural activity and compensation mechanisms is a challenge given the limitation in current neuroimaging modalities and imaging brain activity at a microscopic level. Here we investigate the interplay between various synaptic degeneration and compensation mechanisms, and abnormal cortical oscillations based on a large-scale neural model. Results from the models are consistent with a range of human and animal model findings.

AB - Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with progressive dementia. The clinical symptoms of AD are cognitive and intellectual deficits and behavior dysfunction. EEG has been utilized for diagnosing dementias. There is a strong correlation between cognitive deficit and the degree of the EEG abnormality. EEG spectral analysis in AD patients has shown a decrease in the mean frequency, alpha (8–12 Hz) and beta (13–30 Hz) band powers with a parallel increase in delta (1–3 Hz) and theta (4–7 Hz) band powers compared with those of healthy elderly subjects (Dauwels, Vialatte, & Cichocki, 2011). The EEG abnormalities in AD indicate functional and anatomical impairment of the cerebral cortex affected by the disease. The neuropathology of AD is characterized by an enormous neuronal and synaptic loss in the cerebral cortex and certain subcortical regions, and the formation of pathological proteins (Serrano-Pozo, Frosch, Masliah, & Hyman, 2011). The degree of synaptic loss is the factor most correlated with the severity of AD and cognitive decline (Shankar & Walsh, 2009; Terry et al., 1991). Several experimental studies have found that the neurodegenerative process is accompanied by synaptic compensation mechanisms, “a homeostatic mechanism which maintains the excitatory response of individual neurons and prevents the catastrophic amnesia associated with synapse loss” (Small, 2004; Turrigiano, 2011, 2012). On an activity level, synaptic compensation senses and regulates the firing rate of the network at the neuron or network level (Fröhlich, Bazhenov, & Sejnowski, 2008). Understanding neural activity and compensation mechanisms is a challenge given the limitation in current neuroimaging modalities and imaging brain activity at a microscopic level. Here we investigate the interplay between various synaptic degeneration and compensation mechanisms, and abnormal cortical oscillations based on a large-scale neural model. Results from the models are consistent with a range of human and animal model findings.

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