Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

Kerbler, Georg; Hamlin, Adam; Pannek, Kerstin; Kurniawan, Nyoman D.; Keller, Marianne; Rose, Stephen; Coulson, Elizabeth J.

doi:10.1016/j.neuroimage.2012.10.075

Cited by 26 publications

(29 citation statements)

References 49 publications

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“…Accordingly, the overall magnitude of diffusivity (e.g., MD) was not significantly altered in gray matter regions in 3xTg mice in the present study, consistent with preserved neuronal density in the 3xTg model relative to AD and other mouse models. Our results, however, are in contradiction to several of the aforementioned DTI findings in mouse models of AD [25,26,56] in that FA was decreased in gray matter in 3xTg mice. A notable distinction between the 3xTg model used in the present study and other models is the presence of neurofibrillary tangles in the 3xTg brain, which may account for some of the discrepancies.…”

Section: Discussioncontrasting

confidence: 99%

“…In mice, increased MD, FA, AxD, and RadD were found in an experimental model of forebrain cholinergic neuron loss that mimics AD-related forebrain pathology [56]. Here, DTI metrics were found to correlate inversely with forebrain cholinergic neuron loss.…”

Section: Discussionmentioning

confidence: 60%

“…In the same strain, Zerbi et al [57] found similar results, with increased MD, AxD, and RadD in the hippocampus. Moreover, in mice with a 25% reduction in forebrain cholinergic neurons, mimicking the preferential loss of cholinergic neurons in AD, forebrain diffusivity is increased, with higher MD, FA, AxD, and RadD measures relative to controls [56]. In contrast, a study by Sun et al [23] in APPsw mice, which display a mild AD phenotype characterized by plaque deposition in the absence of other neuropathological characteristics of AD (e.g., tangles or neuron loss), found a decrease in the trace of the diffusion tensor, a directionally averaged diffusion coefficient.…”

Section: Discussionmentioning

confidence: 97%

“…Here, DTI metrics were found to correlate inversely with forebrain cholinergic neuron loss. Diffusivity parameters, however, were collected ex vivo on fixed tissue [56].…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of Alzheimer’s Disease with Diffusion Tensor Imaging

Snow

Dale

O’Brien-Moran

et al. 2017

JAD

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Abstract.A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-␤ (A␤) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinical symptoms, efforts to detect brain changes early could significantly enhance our ability to diagnose AD sooner. Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude, orientation, and anisotropy of the diffusion of water in tissues, has been used to infer neuropathological changes in vivo. Its utility in AD, however, is still under investigation. The current study used DTI to examine brain regions susceptible to AD-related pathology; the cerebral cortex, entorhinal cortex, and hippocampus, in 12-14-month-old 3xTg AD mice that possess both A␤ plaques and neurofibrillary tangles. Mean diffusivity did not differ between 3xTg and control mice in any region. Decreased fractional anisotropy (p < 0.01) and axial diffusivity (p < 0.05) were detected only in the hippocampus, in which both congophilic A␤ plaques and hyperphosphorylated tau accumulation, consistent with neurofibrillary tangle formation, were detected. Pathological tau accumulation was seen in the cortex. The entorhinal cortex was largely spared from AD-related neuropathology. This is the first study to demonstrate DTI abnormalities in gray matter in a mouse model of AD in which both pathological hallmarks are present, suggesting the feasibility of DTI as a non-invasive means of detecting brain pathology in vivo in early-stage AD.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 97%

“…Here, DTI metrics were found to correlate inversely with forebrain cholinergic neuron loss. Diffusivity parameters, however, were collected ex vivo on fixed tissue [56].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of Alzheimer’s Disease with Diffusion Tensor Imaging

Snow

Dale

O’Brien-Moran

et al. 2017

JAD

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show abstract

“…The above physiological effects of ACh are expected to have a beneficial impact on specific functional characteristics of the cortices (Iwamoto et al 2013a). Conversely, a decrease in sensory input and the resulting depression in ACh levels, are expected to impact on and alter specific functional properties of the cortices and promote their dysfunction, as may occur in aging, MCI, and AD (Brueggen et al 2015;Kerbler et al 2013Kerbler et al , 2015.…”

Section: Basal Forebrain (Bfb)-stimulation and Impairmentmentioning

confidence: 99%

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

Daulatzai

2016

Neurotox Res

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Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

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Translational Structural and Functional Signatures of Chronic Alcohol Effects in Mice

Degiorgis¹,

Arefin²,

Ben-Hamida³

et al. 2022

Biological Psychiatry

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Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

Cited by 26 publications

References 49 publications

In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of Alzheimer’s Disease with Diffusion Tensor Imaging

In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of Alzheimer’s Disease with Diffusion Tensor Imaging

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

Translational Structural and Functional Signatures of Chronic Alcohol Effects in Mice

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