Differential Circadian Rhythm Disturbances in Men with Alzheimer Disease and Frontotemporal Degeneration

Harper, David G.; Stopa, Edward G.; McKee, Ann C.; Satlin, Andrew; Harlan, Patricia; Goldstein, Rachel; Volicer, Ladislav

doi:10.1001/archpsyc.58.4.353

Cited by 218 publications

(118 citation statements)

References 54 publications

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“…The few studies which investigated the emotional phenotypes of FTD tau models describe decreased reward-seeking behaviour and increased forced swim test immobility, which Potentially as a result of altered emotionality, PLB2 Tau mice demonstrated a robust hypoactive trait in many experimental parameters, most evident when monitoring circadian and ambient activity within the PhenoTyper. In this respect PLB2 Tau mice present a similar global reduction in activity as observed in human FTD (Harper et al, 2001;Anderson et al, 2009). Hypoactivity and inertia being most pronounced during the initial waking hours, which was also observed here in PLB2 Tau mice.…”

Section: Emotional Phenotypes Of Plb2 Tau Micementioning

confidence: 69%

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Koss

Robinson

Drever

et al. 2016

Neurobiology of Disease

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Models of Tau pathology related to frontotemporal dementia (FTD) are essential to determine underlying neurodegenerative pathologies and resulting Tauopathy relevant behavioural changes. However, existing models are often limited in their translational value due to Tau overexpression, and the frequent occurrence of motor deficits which prevent comprehensive behavioural assessments. In order to address these limitations, a forebrain-specific (CaMKIIα promoter), human mutated Tau (hTauP301L+R406W) knock-in mouse was generated out of the previously characterised PLB1Triple mouse, and named PLB2Tau. After confirmation of an additional hTau species (~60 kDa) in forebrain samples, we identified age-dependent progressive Tau phosphorylation which coincided with the emergence of FTD relevant behavioural traits. In line with the noncognitive symptomatology of FTD, PLB2Tau mice demonstrated early emerging (~ 6 months) phenotypes of heightened anxiety in the elevated plus maze, depressive/apathetic behaviour in a sucrose preference test and generally reduced exploratory activity in the absence of motor impairments. Investigations of cognitive performance indicated prominent dysfunctions in semantic memory, as assessed by social transmission of food preference, and in behavioural flexibility during spatial reversal learning in a homecage corner-learning task. Spatial learning was only mildly affected and task-specific, with impairments at 12-month of age in the corner learning but not in the water maze task. Electroencephalographic (EEG) investigations indicated a vigilance-stage specific loss of alpha power during wakefulness at both parietal and prefrontal recording sites, and site-specific EEG changes during nonrapid eye movement sleep (prefrontal) and rapid eye movement sleep (parietal). Further investigation of hippocampal electrophysiology conducted in slice preparations indicated a modest reduction in efficacy of synaptic transmission in the absence of altered synaptic plasticity. Together, our data demonstrate that the transgenic PLB2Tau mouse model presents with striking behavioural and physiological face validity relevant for FTD, driven by the low level expression of mutant FTD hTau. AbstractModels of Tau pathology related to frontotemporal dementia (FTD) are essential to determine underlying neurodegenerative pathologies and resulting Tauopathy relevant behavioural changes. However, existing models are often limited in their translational value due to Tau overexpression, and the frequent occurrence of motor deficits which prevent comprehensive behavioural assessments. In order to address these limitations, a forebrain-specific (CaMKIIα promoter), human mutated Tau (hTau P301L+R406W ) knock-in mouse was generated out of the previously characterised PLB1 Triple mouse, and named PLB2 Tau . After confirmation of an additional hTau species (~60 kDa) in forebrain samples, we identified age-dependent progressive Tau phosphorylation which was coincided with the emergence of FTD relevant behavioural traits. In...

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Section: Emotional Phenotypes Of Plb2 Tau Micementioning

confidence: 69%

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Koss

Robinson

Drever

et al. 2016

Neurobiology of Disease

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“…Of note, the delayed body temperature minimum in old mouse lemurs contrasts with the phase advance typical of old humans (Monk et al, 1995;Duffy et al, 1998). On the other hand, a delay in body temperature has been observed in demented elderly subjects (Harper et al, 2001), and Duffy et al (Duffy et al, 1998) demonstrated that the body temperature nadir was actually delayed when expressed relative to the waking onset in the elderly. In mouse lemurs, the body temperature minimum was affected by photoperiod but not by age, while the timing of minimal body temperature changed according to age but not photoperiod.…”

Section: ()mentioning

confidence: 98%

Attenuated effect of increased daylength on activity rhythm in the old mouse lemur, a non-human primate

Aujard

Cayetanot

Terrien

et al. 2007

Experimental Gerontology

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To cite this version:Fabienne Aujard, Florence Cayetanot, Jérémy Terrien, Eus J.W. Van Someren. Attenuated effect of increased daylength on activity rhythm in the old mouse lemur, a non-human primate. Experimental Gerontology, Elsevier, 2007, 42 (11) ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ABSTRACTAdaptation of physiological and behavioral functions to seasonal changes in daylength is of major relevance for optimal fitness and survival. Because aging is characterized by changes in biological rhythms, it may be hypothesized that old animals fall short of showing a full adaptation to prolonged changes in the duration of daily light exposure, as naturally occurring in relation to season in younger individuals. To test this hypothesis, we analyzed changes in the patterns of daily locomotor activity and body temperature rhythms of young and old mouse lemurs (Microcebus murinus, Primates) exposed to short and long daylengths. The effect of an increase in the duration of daily light exposure was attenuated in old animals, as compared to younger lemurs. Although some age-related differences in the locomotor activity rhythm could be seen under exposure to short daylength, they were predominant under long daylength. Some mechanisms allowing adaptation to changing day length thus seem to be impaired at old age. Changes in coupling of circadian oscillators to the light-dark cycle and disturbances in the physiological responses to change in light duration should be further investigated.

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“…Van Someren et al (17) reported that rhythms were most fragmented in institutionalized AD patients and that higher levels of daytime activity predicted more coherent rhythms, whereas lower levels of daytime activity predicted rhythm fragmentation. Changes in circadian parameters are not equivalent across different types of dementias; there are differences in the nature and magnitude of rhythm disturbance in AD, frontotemporal dementia, and diffuse Lewy body disease (18). The overall locomotor changes that occur in AD seem to be related to more specific behavioral changes, for example in meal time, which in turn might be linked to poorer nutritional outcomes (19).…”

Section: Functional Studies Of Circadian Disruption In Admentioning

confidence: 99%

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

Coogan

Schutová

Husung

et al. 2013

Biological Psychiatry

148

131

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Alzheimer's disease (AD) is a devastating neurodegenerative condition associated with severe cognitive and behavioral impairments. Circadian rhythms are recurring cycles that display periods of approximately 24 hours and are driven by an endogenous circadian timekeeping system centered on the suprachiasmatic nucleus of the hypothalamus. We review the compelling evidence that circadian rhythms are significantly disturbed in AD and that such disturbance is of significant clinical importance in terms of behavioral symptoms. We also detail findings from neuropathological studies of brain areas associated with the circadian system in postmortem studies, the use of animal models of AD in the investigation of circadian processes, and the evidence that chronotherapeutic approaches aimed at bolstering weakened circadian rhythms in AD produce beneficial outcomes. We argue that further investigation in such areas is warranted and highlight areas for future research that might prove fruitful in ultimately providing new treatment options for this most serious and intractable of conditions.

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Differential Circadian Rhythm Disturbances in Men with Alzheimer Disease and Frontotemporal Degeneration

Cited by 218 publications

References 54 publications

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Attenuated effect of increased daylength on activity rhythm in the old mouse lemur, a non-human primate

The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities

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