P4-080: Pharmacologic Inhibition of Rock1 and Rock2 Reverses Dendritic Spine Morphology Abnormalities Associated with Age-Related Memory Loss and Alzheimer’s Disease

2016 ◽  
Vol 12 ◽  
pp. P1043-P1044
Author(s):  
Benjamin W. Henderson ◽  
Erik G. Gentry ◽  
Travis Rush ◽  
Jeremy H. Herskowitz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spine ◽  
Memory Loss ◽  
Spine Morphology ◽  
Age Related ◽  
Dendritic Spine Morphology ◽  
Pharmacologic Inhibition

Clinical course of Alzheimer’s disease

2011 ◽  
Author(s):  
Alberto Lleo ◽  
Rafael Blesa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Daily Living ◽  
Clinical Course ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Remote Memory ◽  
Initial Symptom ◽  
Delayed Recall ◽  
Age Related

• Alzheimer’s disease is an age-related neurodegenerative disorder, with onset usually in late life, characterized by cognitive impairment, a variety of behavioural symptoms, and restrictions in the activities of daily living• The initial symptom is episodic memory loss, in particular in delayed recall of visual and/or verbal material. Immediate and remote memory is usually preserved in early stages...

Age-Associated Memory Loss: Initial Neuropsychological and Cerebral Metabolic Findings of a Longitudinal Study

1994 ◽  
Vol 6 (1) ◽  
pp. 23-44 ◽  
Author(s):  
Gary W. Small ◽  
Anna Okonek ◽  
Mark A. Mandelkern ◽  
Asenath La Rue ◽  
Linda Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Longitudinal Study ◽  
Cognitive Abilities ◽  
Mood State ◽  
Familial Risk ◽  
Memory Loss ◽  
Subjective Memory ◽  
Age Related ◽  
Positron Emission

To determine the relationships between clinical and brain function in persons with a familial risk for Alzheimer's disease, the authors assessed subjective and objective cognitive abilities, mood state, and cerebral glucose metabolism (using positron emission tomography) in 43 persons with age-associated memory impairment, with and without first-degree relatives with a clinical diagnosis of Alzheimer's disease. Subjective complaints of memory loss, mood state ratings, and objective memory measures were similar in persons with a family history of Alzheimer's disease (n = 29) compared to those without such a history (n = 14). Metabolic ratios in the frontal regions correlated with a decrease in a specific type of subjective memory complaint (mnemonics usage; p < .001) and some mood state ratings. These results indicate that parietal and temporal hypometabolism is not evident in persons with mild age-related memory complaints, even when such subjects have a familial risk for Alzheimer's disease. Moreover, self-reports of mnemonics usage may be sensitive indicators of decreased frontal lobe function. Longitudinal study will determine whether such clinical and metabolic measures will predict eventual disease progression.

scholarly journals EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Lindsay Poppe ◽  
Laura Rué ◽  
Mieke Timmers ◽  
Annette Lenaerts ◽  
Annet Storm ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dendritic Spine ◽  
Cognitive Functions ◽  
Social Memory ◽  
Beta Amyloid ◽  
Amyloid Peptide ◽  
Spine Morphology ◽  
Model Of Alzheimer’S Disease

Abstract Background EphA4 is a receptor of the ephrin system regulating spine morphology and plasticity in the brain. These processes are pivotal in the pathophysiology of Alzheimer’s disease (AD), characterized by synapse dysfunction and loss, and the progressive loss of memory and other cognitive functions. Reduced EphA4 signaling has been shown to rescue beta-amyloid-induced dendritic spine loss and long-term potentiation (LTP) deficits in cultured hippocampal slices and primary hippocampal cultures. In this study, we investigated whether EphA4 ablation might preserve synapse function and ameliorate cognitive performance in the APPPS1 transgenic mouse model of AD. Methods A postnatal genetic ablation of EphA4 in the forebrain was established in the APPPS1 mouse model of AD, followed by a battery of cognitive tests at 9 months of age to investigate cognitive function upon EphA4 loss. A Golgi-Cox staining was used to explore alterations in dendritic spine density and morphology in the CA1 region of the hippocampus. Results Upon EphA4 loss in APPPS1 mice, we observed improved social memory in the preference for social novelty test without affecting other cognitive functions. Dendritic spine analysis revealed altered synapse morphology as characterized by increased dendritic spine length and head width. These modifications were independent of hippocampal plaque load and beta-amyloid peptide levels since these were similar in mice with normal versus reduced levels of EphA4. Conclusion Loss of EphA4 improved social memory in a mouse model of Alzheimer’s disease in association with alterations in spine morphology.

Optimizing Modifiable and Lifestyle-related Factors in the Prevention of Dementia Disorders with Special Reference to Alzheimer, Parkinson and Autism Diseases

2020 ◽  
Vol 16 (6) ◽  
pp. 900-911
Author(s):  
Umesh C. Gupta ◽  
Subhas C. Gupta
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Pollutants ◽  
Memory Loss ◽  
Tau Proteins ◽  
Body Parts ◽  
Related Factors ◽  
Age Related ◽  
Major Factors

Dementia is a syndrome and an umbrella term that encompasses Alzheimer, Parkinson and autism diseases. These diseases are by far the most common cause of dementia; therefore this investigation will chiefly include these disorders, with a limited discussion of few other disorders related to dementia. Alzheimer’s disease (AD) is characterized by the accumulation of cerebral β-amyloid plaques, tau proteins and memory loss; Parkinson by the deterioration of brain cells which regulate the movement of body parts and produce dopamine; and autism by abnormalities of social disorder and difficulty in communicating and forming relationships. Alzheimer’s disease and cognitive impairment in dementia are age-related and manageable only with early diagnosis and prevention. Data based on several decades of research has shown that the major factors responsible for the induction of inflammation in dementia and many chronic diseases are infections, obesity, alcohol, radiation, environmental pollutants, improper nutrition, lack of physical activity, depression, anxiety, genetic factors, and sleep deprivation. There are some studied preventive measures for dementia including continued physical activity and consuming predominantly a plant-based Mediterranean diet comprising olive oil and foods containing flavonoids and other phytochemicals having strong antioxidant and anti-inflammatory properties and along with management of chronic conditions.

scholarly journals Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1308
Author(s):  
Shang-Der Chen ◽  
Jenq-Lin Yang ◽  
Yi-Heng Hsieh ◽  
Tsu-Kung Lin ◽  
Yi-Chun Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Memory Loss ◽  
Oxygen Species ◽  
Mechanistic Target Of Rapamycin ◽  
Cell Cycle Reentry ◽  
Age Related ◽  
Reduce Activity

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

scholarly journals Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1983
Author(s):  
Erika Kropf ◽  
Margaret Fahnestock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Basal Forebrain ◽  
Memory Loss ◽  
Reactive Oxygen ◽  
Neurotrophin Receptor ◽  
Nitrogen Species ◽  
Age Related ◽  
The Brain

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

scholarly journals Collapsin Response Mediator Proteins: Novel Targets for Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 949-960 ◽  
Author(s):  
Tam T. Quach ◽  
Aubin Moutal ◽  
Rajesh Khanna ◽  
Nicholas P. Deems ◽  
Anne-Marie Duchemin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axon Guidance ◽  
Immune Cells ◽  
Dendritic Growth ◽  
Therapeutic Interventions ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
Postmortem Studies ◽  
Novel Targets

Numerous experimental and postmortem studies have increasingly reported dystrophic axons and dendrites, and alterations of dendritic spine morphology and density in the hippocampus as prominent changes in the early stages of Alzheimer’s disease (AD). Furthermore, these alterations tend to correlate well with the progressive cognitive decline observed in AD. For these reasons, and because these neurite structures have a capacity to re-grow, re-establish lost connections, and are critical for learning and memory, there is compelling evidence to suggest that therapeutic interventions aimed at preventing their degradation or promoting their regrowth may hold tremendous promise in preventing the progression of AD. In this regard, collapsin response mediator proteins (CRMPs), a family of phosphoproteins playing a major role in axon guidance and dendritic growth, are especially interesting. The roles these proteins play in neurons and immune cells are reviewed here.

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