Alzheimer’s Disease: The Alternative Serotonergic Hypothesis of Cognitive Decline

Vakalopoulos, Costa

doi:10.3233/jad-170364

Cited by 29 publications

(17 citation statements)

References 57 publications

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“…No experimental study, however, has yet provided evidence of a significant structural or functional change in this nucleus at the preclinical stage of AD. At present, this link has only been hypothesised 9 .…”

Section: Introductionmentioning

confidence: 94%

Reduced monoaminergic nuclei MRI signal detectable in pre-symptomatic older adults with future memory decline

Venneri

Marco

2020

Sci Rep

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Evidence from murine models and human post-mortem studies indicates that monoaminergic nuclei undergo degeneration at the pre-symptomatic stage of Alzheimer’s disease (AD). Analysing 129 datasets from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and relying on the Clinical Dementia Rating as group-defining instrument, we hypothesised that the MRI signal of monoaminergic nuclei would be a statistically significant predictor of memory decline in participants initially recruited in ADNI as healthy adults. As opposed to a group of cognitively stable participants, participants developing memory decline had reduced signal in the ventral tegmental area at baseline, before any evidence of functional decline emerged. These findings indicate that monoaminergic degeneration predates the onset of memory decline in an AD-centred initiative, with a crucial involvement of very-early changes of a dopaminergic region. This translates into potential informative avenues for pharmacological treatment of pre-symptomatic AD.

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Section: Introductionmentioning

confidence: 94%

Reduced monoaminergic nuclei MRI signal detectable in pre-symptomatic older adults with future memory decline

Venneri

Marco

2020

Sci Rep

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“…Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases of the CNS, characterized by memory loss and cognitive dysfunction, and has a variety of neurological and psychiatric symptoms and behavioral disorders [45]. Pathologically, AD is marked by the presence of extracellular amyloid plaques (APs) and intracellular neurofibrillary tangles (NFTs) in the brain.…”

Section: Astrocytes Morphology and Functions In The Cnsmentioning

confidence: 99%

Reactive Astrocytes in Neurodegenerative Diseases

Li¹,

Li²,

Zheng³

et al. 2019

Aging and disease

293

225

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Astrocytes, the largest and most numerous glial cells in the central nervous system (CNS), play a variety of important roles in regulating homeostasis, increasing synaptic plasticity and providing neuroprotection, thus helping to maintain normal brain function. At the same time, astrocytes can participate in the inflammatory response and play a key role in the progression of neurodegenerative diseases. Reactive astrocytes are strongly induced by numerous pathological conditions in the CNS. Astrocyte reactivity is initially characterized by hypertrophy of soma and processes, triggered by different molecules. Recent studies have demonstrated that neuroinflammation and ischemia can elicit two different types of reactive astrocytes, termed A1s and A2s. However, in the case of astrocyte reactivity in different neurodegenerative diseases, the recently published research issues remain a high level of conflict and controversy. So far, we still know very little about whether and how the function or reactivity of astrocytes changes in the progression of different neurodegenerative diseases. In this review, we aimed to briefly discuss recent studies highlighting the complex contribution of astrocytes in the process of various neurodegenerative diseases, which may provide us with new prospects for the development of an excellent therapeutic target for neurodegenerative diseases.

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“…Inhibition of the dorsal raphe nucleus, the main serotonin source, alters impulsivity by reducing tolerance to delayed rewards and enhancing avoidance of difficulty selection 30,31 . As AD progresses, loss of serotonergic neurons and/or hyperphosphorylation of tau proteins accompany local neuroinflammation in the dorsal raphe 8,9,32,33 . Besides, as a result of re-analysis including a confound regressor (the number of motor response in each trial), hyperactivation of the dorsal raphe nucleus in AD model mice was observed as well.…”

Section: Discussionmentioning

confidence: 99%

Hyper BOLD Activation in Dorsal Raphe Nucleus of APP/PS1 Alzheimer’s Disease Mouse during Reward-Oriented Drinking Test under Thirsty Conditions

Sakurai

Shintani

Jomura

et al. 2020

Sci Rep

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Alzheimer's disease (AD), a neurodegenerative disease, causes behavioural abnormalities such as disinhibition, impulsivity, and hyperphagia. preclinical studies using AD model mice have investigated these phenotypes by measuring brain activity in awake, behaving mice. in this study, we monitored the behavioural alterations of impulsivity and hyperphagia in middle-aged AD model mice. As a behavioural readout, we trained the mice to accept a water-reward under thirsty conditions. to analyse brain activity, we developed a measure for licking behaviour combined with visualisation of whole brain activity using awake fMRI. In a water-reward learning task, the AD model mice showed significant hyperactivity of the dorsal raphe nucleus in thirsty conditions. in summary, we successfully visualised altered brain activity in AD model mice during reward-oriented behaviour for the first time using awake fMRi. this may help in understanding the causes of behavioural alterations in AD patients.Fifty million people worldwide currently suffer from dementia. This number is estimated to reach 130 million by 2050. Alzheimer's disease (AD) is a neurodegenerative disease accounting for 60-70% of dementia cases 1 . AD develops through amnestic mild cognitive impairment (MCI), in which a decrease of memory function is the only symptom can be recognised. Once dementia develops, memory and various cognitive functions decrease, behavioural and psychological symptoms of dementia (BPSP) are also exhibited 1-3 . As these symptoms progress, it becomes impossible to maintain an independent daily life. Dementia patients mostly need medical care due to BPSP rather than reducing of memory and cognitive functions. BPSP includes depression, anxiety, and apathy. Although research on these BPSP symptoms has progressed, however, most symptoms such as disinhibition, impulsivity and hyperphagia have not been analysed in the way of pathology.AD significantly impairs reward-based behaviour (by 15-20%) in patients. A typical example is hyperphagia, which stems from a lack of satiety control, similar to disorders of impulsivity and compulsivity 4,5 . The Urgency, lack of Perseverance, lack of Premeditation, Sensation Seeking (UPPS) Scale or Barrat's Impulsiveness Scale (BIS) are now used to test for impulsivity in AD patients 3 . Overeating and impulsivity have also recently been reported in AD model mice 6,7 . These observations suggest that AD mice models may be useful in studying hyperphagia and early changes in impulsive behaviour. It has also been suggested that the brainstem serotonergic system, including the dorsal raphe nucleus 8,9 and ventral temporal lobe (hippocampus, parahippocampus, amygdala), are involved in such alterations. However, the neurological mechanisms behind these phenotypes have not yet been identified. In order to elucidate these mechanistic underpinnings, direct evaluation of brain activity associated with abnormal behaviour phenotypes is required 10 .Functional magnetic resonance imaging (fMRI) is widely used in neuroscience resea...

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Alzheimer’s Disease: The Alternative Serotonergic Hypothesis of Cognitive Decline

Cited by 29 publications

References 57 publications

Reduced monoaminergic nuclei MRI signal detectable in pre-symptomatic older adults with future memory decline

Reduced monoaminergic nuclei MRI signal detectable in pre-symptomatic older adults with future memory decline

Reactive Astrocytes in Neurodegenerative Diseases

Hyper BOLD Activation in Dorsal Raphe Nucleus of APP/PS1 Alzheimer’s Disease Mouse during Reward-Oriented Drinking Test under Thirsty Conditions

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