Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of Alzheimer's disease

Kara, Firat; Belloy, Michaël E.; Voncken, Rick; Sarwari, Zahra; Yadav, Govind; Anckaerts, Cynthia; Langbeen, A.; Leysen, Valérie; Shah, Disha; Jacobs, Jules; Hamaide, Julie; Bols, P.E.J.; Audekerke, Johan Van; Daans, Jasmijn; Guglielmetti, Caroline; Kantarci, Kejal; Prévot, Vincent; Rößner, Steffen; Ponsaerts, Peter; Linden, Annemie Van der; Verhoye, Marleen

doi:10.1016/j.neurobiolaging.2021.02.011

Cited by 9 publications

(11 citation statements)

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“…Both time-of-flight MRA and CE MRA have been applied in amyloidosis animal models (Table 3). Detection of vascular alterations by in vivo MRA and histology has been reported in APP/PS1, arcAβ, APP/PS1, APP23 mice [39,118,128,152,153]. Klohs et al demonstrated and reduced density and remodeling of cerebral microvasculature by using CE MRA reveals in aged arcAβ mice [152](Figure 2e-h).…”

Section: Mr Angiography (Mra)mentioning

confidence: 65%

“…MRS has been shown detecting the distinct metabolic profiles in APP/PS1 mice [121][122][123][124][125][126], J20 mice [109], APPswe mice [127,128] compared to wild-type mice respectively. Several studies have reported reduced N-acetylaspartate /creatine ratio [125] and [124], lower glutamate levels [123] in APP/PS1 mice compared to wild-type mice.…”

Section: Mrsmentioning

confidence: 99%

“…5×FAD mice [135] MRS TgF344 rats [132] J20 mice [109] APP/PS1 mice [121][122][123][124][125][126] 5×FAD mice [130] 3×Tg mice [129] APPswe mice [127,128]. APP/PS2/Tau mice [131] TASTPM mice [131,167] APP/PS1 mice [105,125,164,168,236] McGill-R-Thy1-APP rats [162] mice [250,251] APP-Au mice [252] 3×Tg mice [93,165,253] APPswe mice [244] APP/PS1KI mice [166] APP/TTA mice [254] DKI APP/PS1 mice [184] 3×Tg mice [188] qMTI APPswe mice [178] DTI TgF344 rats [183] APPswe mice [175,178,186,255] PDAPP mice [176] App NL-G-F knock-in mice [72] APP/PS1 mice [123,171,179,187,189,256] APP23 ...…”

Section: Declaration Of Interestmentioning

confidence: 99%

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Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Ni¹

2021

Preprint

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Amyloid-beta plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant amyloid-beta and tau accumulation induce neuroinflammation, cerebrovascular alterations, synaptic deficits, functional deficits, and neurodegeneration, leading to cognitive impairment. Animal models recapitulating the amyloid-beta pathology such as transgenic, knock-in mouse and rat models have facilitated the understanding of disease mechanisms and development of therapeutics targeting at amyloid-beta. There is a rapid advance in high-field MR in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences such as diffusion tensor imaging, arterial spin labelling, resting-state functional MRI, anatomical MRI, MR spectroscopy as well as contrast agents have been developed for the applications in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole brain field-of-view. MRI have been utilized to visualize non-invasively the amyloid-beta deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, cerebrovascular and glymphatic system in animal models of amyloidosis. Many of the readouts are translational in clinical MRI in the brain of patients with Alzheimer’s disease. In this review, we summarize the recent advance of using MRI for visualizing the pathophysiology in amyloidosis animal model. We discuss the outstanding challenges in brain imaging using MRI in small animal and propose future outlook in visualizing amyloid-beta-related alterations in brain of animal models.

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Section: Mr Angiography (Mra)mentioning

confidence: 65%

Section: Mrsmentioning

confidence: 99%

Section: Declaration Of Interestmentioning

confidence: 99%

See 1 more Smart Citation

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Ni¹

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…MRS has been shown to detect the distinct metabolic profiles in APP/PS1 [ 121 , 147 , 148 , 149 , 150 , 151 ], and APPswe mice [ 115 , 154 ] compared to wild-type mice. Several studies have reported a reduced N-acetylaspartate/creatine ratio [ 148 , 149 ] and a lower glutamate level in APP/PS1 mice compared to wild-type mice [ 121 ].…”

Section: Neurochemical Changes Detectionmentioning

confidence: 99%

“…Both time-of-flight and contrast-enhanced (CE)-MRA have been applied in amyloidosis animal models ( Table 3 ). The detection of vascular alterations by in vivo MRA and histology has been reported in APP/PS1, arcAβ, APP/PS1, and APP23 mice [ 30 , 115 , 134 , 136 , 156 ]. Klohs et al demonstrated a reduced density and remodeling of cerebral microvasculature in aged arcAβ mice compared to wild-type mice by using CE-MRA [ 156 ] ( Figure 2 e–h).…”

Section: Cerebrovascular Imagingmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

2021

IJMS

View full text Add to dashboard Cite

Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.

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Premenopausal bilateral oophorectomy and brain white matter brain integrity in later‐life

Mielke,

Frank,

Christenson

et al. 2024

Alzheimer's & Dementia

Self Cite

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INTRODUCTIONPremenopausal bilateral oophorectomy (PBO) is associated with later‐life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity.METHODSFemale participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO < 40 years; 43 with PBO 40‐45 years; 39 with PBO 46‐49 years; 907 referents without PBO < 50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype.RESULTSFemales with PBO < 40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto‐occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity.DISCUSSIONFemales who underwent PBO < 40 years had reduced white matter integrity across multiple regions in later‐life. These results are important for females considering PBO for noncancerous conditions.Highlights Females with premenopausal bilateral oophorectomy (PBO) < 40 years had lower FA versus referents. Females with PBO < 40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45‐49 years also had some white matter changes versus referents.

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Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of Alzheimer's disease

Cited by 9 publications

References 91 publications

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Premenopausal bilateral oophorectomy and brain white matter brain integrity in later‐life

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