Cognitive and Sensorimotor Tasks for Assessing Functional Impairments in Mouse Models of Alzheimer’s Disease and Related Disorders

Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right temporal regions. How lateralisation of temporal lobe pathology impacts the hedonic experience in SD remains largely unknown yet has important implications for understanding socioemotional and functional impairments in this syndrome. Here, we explored how lateralisation of temporal lobe atrophy impacts anhedonia severity on the Snaith–Hamilton Pleasure Scale in 28 SD patients presenting with variable right- (SD-R) and left-predominant (SD-L) profiles of temporal lobe atrophy compared to that of 30 participants with Alzheimer’s disease and 30 healthy older Control participants. Relative to Controls, SD-R but not SD-L or Alzheimer’s patients showed clinically significant anhedonia, representing a clear departure from premorbid levels. Overall, anhedonia was more strongly associated with functional impairment on the Frontotemporal Dementia Functional Rating Scale and motivational changes on the Cambridge Behavioural Inventory in SD than in Alzheimer’s disease patients. Voxel-based morphometry analyses revealed that anhedonia severity correlated with reduced grey matter intensity in a restricted set of regions centred on right orbitofrontal and temporopolar cortices, bilateral posterior temporal cortices, as well as the anterior cingulate gyrus and parahippocampal gyrus, bilaterally. Finally, regression and mediation analysis indicated a unique role for right temporal lobe structures in modulating anhedonia in SD. Our findings suggest that degeneration of predominantly right-hemisphere structures deleteriously impacts the capacity to experience pleasure in SD. These findings offer important insights into hemispheric lateralisation of motivational disturbances in dementia and suggest that anhedonia may emerge at different timescales in the SD disease trajectory depending on the integrity of the right hemisphere.

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A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer’s disease

Molecular Neurodegeneration ◽

10.1186/s13024-016-0103-6 ◽

2016 ◽

Vol 11 (1) ◽

Cited By ~ 17

Author(s):

Jia Luo ◽

Sue H. Lee ◽

Lawren VandeVrede ◽

Zhihui Qin ◽

Manel Ben Aissa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Models ◽

Therapeutic Approach ◽

Disease Modification ◽

Model Of Alzheimer’S Disease

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Oleic Acid Ameliorates Amyloidosis in Cellular and Mouse Models of Alzheimer's Disease

Brain Pathology ◽

10.1111/j.1750-3639.2010.00449.x ◽

2010 ◽

Vol 21 (3) ◽

pp. 321-329 ◽

Cited By ~ 57

Author(s):

Zareen Amtul ◽

David Westaway ◽

David F. Cechetto ◽

Richard F. Rozmahel

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Oleic Acid ◽

Mouse Models

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Astrocyte Reactivity in Alzheimer’s Disease: Therapeutic Opportunities to Promote Repair

Current Alzheimer Research ◽

10.2174/1567205018666211029164106 ◽

2021 ◽

Vol 18 ◽

Author(s):

Nazanin Mirzaei ◽

Nicola Davis ◽

Tsz Wing Chau ◽

Magdalena Sastre

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Mouse Models ◽

Neurodegenerative Disorders ◽

Amyloid Β ◽

Neuroprotective Effects ◽

Synaptic Density ◽

Inflammatory Profile

: Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer’s disease (AD), with the prominent presence of reactive astrocytes sur- rounding amyloid β- plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demon- strated that astrocytes from AD brains are different from “normal” healthy astrocytes, showing dys- regulations in areas such as neurotransmitter recycling, including glutamate and GABA, and im- paired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology as well as in the inflammatory profile and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal mod- els has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.

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