Motor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer’s disease

O’Leary, Timothy P.; Robertson, Amanda; Chipman, Peter H.; Rafuse, Victor F.; Brown, Richard E.

doi:10.1016/j.bbr.2017.09.009

Cited by 86 publications

(100 citation statements)

References 48 publications

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“…Of all the measures used, we found a clear age‐related decline and largest effect sizes with latency to fall on the rotarod, which suggests the rotarod may be especially useful for future preclinical studies using the 5xFAD mouse. Furthermore, age‐related motor impairments on the rotarod have been replicated in other studies and is amenable to therapeutic intervention, as environmental enrichment corrects this impairment in 5xFAD mice . Impaired performance in 5xFAD mice on the balance beam has also been reliably found across studies and shows an age‐related decline, and thus is also a valuable addition to future work with 5xFAD mice.…”

Section: Discussionmentioning

confidence: 73%

“…Previous studies documenting motor dysfunction in 5xFAD mice have used only one sex of 5xFAD mice, and this is the first study to examine sex differences in motor impairments. Consistent with previous studies, we reliably detected motor impairment in both male and female 5xFAD mice, and found that age‐related progression of motor impairment was generally consistent across sexes.…”

Section: Discussionmentioning

confidence: 99%

“…This study tested male and female wild‐type (WT) and 5xFAD mice between 3 and 16 months of age. The 3‐16 months age range was selected because very few behavioral phenotypes are reported prior to 3 months and after 16 months 5xFAD mice have pronounced motor impairment . Mice were the progeny of male hemizygous C57BL/6J × SJL/J FN 5xFAD (B6SJL‐Tg (APPSwFILon, PSEN1*M146L*L286V) 6799Vas/Mmjax) and female WT C57BL/ 6J × SJL/J F1 mice obtained from Jackson Laboratories (Bar Harbour, Maine) and bred in our laboratory.…”

Section: Methodsmentioning

confidence: 99%

“…The transgenic 5xFAD mouse develops many pathological changes observed in AD including cognitive impairment a rapid development of Aβ‐plaques, astro‐ and micro‐gliosis, cortical cell loss and reduced cerebral glucose uptake . The 5xFAD mouse also shows motor dysfunction after 9 months of age . Therefore, the 5xFAD mouse may be a particularly useful animal model to examine the development of motor dysfunction in AD, and these motor deficits may be useful in the assessment of novel therapeutics.…”

Section: Introductionmentioning

confidence: 99%

“…Because motor function is not a unitary process, a battery of different tests must be used to detect dysfunction within the varied motor control systems of the brain and spinal cord . Previous studies with 5xFAD mice have shown reduced body weight, along with impairments in motor coordination, balance, grip strength and gait beginning between 9 and 12 months of age . These motor impairments are thought to be due to the development of Aβ‐related pathology within the pyramidal and extra‐pyramidal motor systems of the brain and spinal cord, rather than dysfunction within the peripheral nervous system …”

Section: Introductionmentioning

confidence: 99%

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Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

O’Leary

Mantolino

Stover

et al. 2018

Genes Brain and Behavior

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Alzheimer's disease (AD) is a neurodegenerative disorder that leads to age‐related cognitive and sensori‐motor dysfunction. There is an increased understanding that motor dysfunction contributes to overall AD severity, and a need to ameliorate these impairments. The 5xFAD mouse develops the neuropathology, cognitive and motor impairments observed in AD, and thus may be a valuable animal model to study motor deficits in AD. Therefore, we assessed age‐related changes in motor ability of male and female 5xFAD mice from 3 to 16 months of age, using a battery of behavioral tests. At 9‐10 months, 5xFAD mice showed reduced body weight, reduced rearing in the open‐field and impaired performance on the rotarod compared to wild‐type controls. At 12‐13 months, 5xFAD mice showed reduced locomotor activity on the open‐field, and impaired balance on the balance beam. At 15‐16 months, impairments were also seen in grip strength. Although sex differences were observed at specific ages, the development of motor dysfunction was similar in male and female mice. Given the 5xFAD mouse is commonly on a C57BL/6 × SJL hybrid background, a subset of mice may be homozygous recessive for the Dysf im mutant allele, which leads to muscular weakness in SJL mice and may exacerbate motor dysfunction. We found small effects of Dysf im on motor function, suggesting that Dysf im contributes little to motor dysfunction in 5xFAD mice. We conclude that the 5xFAD mouse may be a useful model to study mechanisms that produce motor dysfunction in AD, and to assess the efficacy of therapeutics on ameliorating motor impairment.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

O’Leary

Mantolino

Stover

et al. 2018

Genes Brain and Behavior

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Degradation of Bone Quality in a Transgenic Mouse Model of Alzheimer′s Disease

LLabre

Gil

Amatya

et al. 2020

Journal of Bone and Mineral Research

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Alzheimer′s disease (AD) patients present with symptoms such as impairment of insulin signaling, chronic inflammation, and oxidative stress. Furthermore, there are comorbidities associated with AD progression. For example, osteoporosis is common with AD wherein patients exhibit reduced mineralization and a risk for fragility fractures. However, there is a lack of understanding on the effects of AD on bone beyond loss of bone density. To this end, we investigated the effects of AD on bone quality using the 5XFAD transgenic mouse model in which 12‐month‐old 5XFAD mice showed accumulation of amyloid‐beta (Aβ42) compared with wild‐type (WT) littermates (n = 10/group; 50% female, 50% male). Here, we observed changes in cortical bone but not in cancellous bone quality. Both bone mass and bone quality, measured in femoral samples using imaging (micro‐CT, confocal Raman spectroscopy, X‐ray diffraction [XRD]), mechanical (fracture tests), and chemical analyses (biochemical assays), were altered in the 5XFAD mice compared with WT. Micro‐CT results showed 5XFAD mice had lower volumetric bone mineral density (BMD) and increased endocortical bone loss. XRD results showed decreased mineralization with smaller mineral crystals. Bone matrix compositional properties, from Raman, showed decreased crystallinity along with higher accumulation of glycoxidation products and glycation products, measured biochemically. 5XFAD mice also demonstrated loss of initiation and maximum toughness. We observed that carboxymethyl‐lysine (CML) and mineralization correlated with initiation toughness, whereas crystal size and pentosidine (PEN) correlated with maximum toughness, suggesting bone matrix changes predominated by advanced glycation end products (AGEs) and altered/poor mineral quality explained loss of fracture toughness. Our findings highlight two pathways to skeletal fragility in AD through alteration of bone quality: (i) accumulation of AGEs; and (ii) loss of crystallinity, decreased crystal size, and loss of mineralization. We observed that the accumulation of amyloidosis in brain correlated with an increase in several AGEs, consistent with a mechanistic link between elevated Aβ42 levels in the brain and AGE accumulation in bone. © 2022 American Society for Bone and Mineral Research (ASBMR).

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Tactile stimulation improves cognition, motor, and anxiety‐like behaviors and attenuates the Alzheimer's disease pathology in adult APP^{NL‐G‐F/NL‐G‐F} mice

Hossain

Karem

Jafari

et al. 2022

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Motor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer’s disease

Cited by 86 publications

References 48 publications

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

Degradation of Bone Quality in a Transgenic Mouse Model of Alzheimer′s Disease

Tactile stimulation improves cognition, motor, and anxiety‐like behaviors and attenuates the Alzheimer's disease pathology in adult APP^{NL‐G‐F/NL‐G‐F} mice

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Motor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer’s disease

Cited by 86 publications

References 48 publications

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

Degradation of Bone Quality in a Transgenic Mouse Model of Alzheimer′s Disease

Tactile stimulation improves cognition, motor, and anxiety‐like behaviors and attenuates the Alzheimer's disease pathology in adult APPNL‐G‐F/NL‐G‐F mice

Contact Info

Product

Resources

About

Tactile stimulation improves cognition, motor, and anxiety‐like behaviors and attenuates the Alzheimer's disease pathology in adult APP^{NL‐G‐F/NL‐G‐F} mice