Genetics of Neurodegenerative Diseases

2016 ◽  
Author(s):  
Lynn M. Bekris ◽  
James B. Leverenz
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Neurodegenerative Disorders ◽  
Genetic Variants ◽  
Dementia With Lewy Bodies ◽  
Autosomal Dominant ◽  
Lewy Bodies ◽  
Genetic Knowledge ◽  
Dominant Mutation ◽  
Time Line

A great deal has been discovered about Neurodegenerative disorders (NDDs) including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, dementia with Lewy bodies . This includes genetic variants associated with both sporadic and autosomal dominant NDDs. These findings have been crucial in our understanding the underlying factors that drive neuropathological changes and in clarifying the time line of biomarker changes in presymptomatic autosomal dominant mutation carriers. While much is still to be learned, these findings will play an important role in the future of neurodegenerative prediction, diagnosis, and treatment. This chapter summarizes the current genetic knowledge related to both the sporadic and autosomal dominant forms of neurodegenerative disease.

scholarly journals Lost in a Dream

2019 ◽  
pp. 381-396
Author(s):  
Carlos L. Rodriguez ◽  
Babak Tousi
Keyword(s):  
Motor Neurons ◽  
Neurodegenerative Disorders ◽  
Dementia With Lewy Bodies ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Behavior Disorder ◽  
Sleep Behavior ◽  
The Relationship ◽  
Over Time

Rapid-eye-movement sleep behavior disorder (RBD) is a parasomnia that is closely associated with neurodegenerative disorders. RBD is usually caused by neurodegeneration within the brainstem that disables the system responsible for immobilizing skeletal muscles during REM sleep and thus permits motor neurons to activate these muscles during dreaming. The underlying source of the brainstem neurodegeneration spreads over time to other central nervous system regions until it has sufficiently evolved to permit clinical recognition of the underlying neurodegenerative disorder. Longitudinal follow-up of patients with RBD has demonstrated that most patients subsequently develop some neurodegenerative disorder years later, particularly the synucleinopathies. We review the relationship between RBD and dementia with Lewy bodies, which is one of the synucleinopathies. The management of RBD is reviewed with discussion of the relevant considerations in patients with dementia with Lewy bodies.

Immunotherapy for Neurodegenerative Disorders

2016 ◽  
Author(s):  
David Morgan
Keyword(s):  
At Risk ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Neurodegenerative Disorders ◽  
Health Concern ◽  
Cultured Neurons ◽  
Preclinical Data ◽  
Age Related ◽  
The World ◽  
Disease Modifying

Neurodegenerative diseases are a growing health concern through the world as gains in longevity result in an increased population at risk of these age-related disorders. Unfortunately no disease modifying treatments exist for these disorders. Over the last three decades enormous insights have been gained into the causes of these disorders. One approach to treating these diseases is to direct immunotherapy against the misfolded proteins that accumulate within the brains of those with neurodegenerative disease in an attempt to clear the accumulating proteins and slow or prevent expression of the disease. This chapter summarizes the recent (and frustrating) experience with anti-Aβ‎ immunotherapy to treat mild to moderate Alzheimer’s disease, and holds hope that newer generation antibodies and treating presymptomatic disease will have greater impact. In addition, it reviews the preclinical data regarding approaches to treating tau, synuclein, and prion disorders, all of which demonstrate consistent effects in mice and cultured neurons.

Sleep disorders in neurodegenerative diseases other than Parkinson disease and multiple system atrophy

2017 ◽  
Author(s):  
Raffaele Manni ◽  
Michele Terzaghi
Keyword(s):  
Neurodegenerative Diseases ◽  
Sleep Disorders ◽  
Neurodegenerative Disorders ◽  
Sleep Problems ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Spinocerebellar Ataxias ◽  
Age Related ◽  
Key Points ◽  
Sleep Alterations

This chapter examines sleep–wake disturbances occurring in the most common neurodegenerative disorders. It reviews sleep alterations in Alzheimer disease and dementia with Lewy bodies. It also discusses sleep problems in progressive supranuclear palsy, corticobasal degeneration, Huntington disease, and spinocerebellar ataxias. Status dissociatus as an extreme form of sleep alteration in advanced neurodegenerative diseases is also considered. The chapter reviews the key points for the treatment of disrupted sleep in neurodegenerative disorders, with a focus on pharmacological and nonpharmacological interventions to improve sleep continuity. It also summarizes paraphysiological age-related changes in sleep patterns and discusses indications and procedures for clinical and instrumental assessment of sleep disorders in neurodegenerative disorders.

scholarly journals Molecular mechanisms of proteinopathies across neurodegenerative disease: a review

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Alexander P. Marsh
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Current Data ◽  
Main Body ◽  
Molecular Events ◽  
Underlying Pathology

Abstract Background Although there is a range of different symptoms across neurodegenerative diseases, they have been noted to have common pathogenic features. An archetypal feature shared between these diseases is protein misfolding; however, the mechanism behind the proteins abnormalities is still under investigation. There is an emerging hypothesis in the literature that the mechanisms that lead to protein misfolding may be shared across neurodegenerative processes, suggesting a common underlying pathology. Main body This review discusses the literature to date of the shared features of protein misfolding, failures in proteostasis, and potential propagation pathways across the main neurodegenerative disorders. Conclusion The current data suggests, despite overarching processes being shared, that the molecular events implicated in protein pathology are distinct across common neurodegenerative disorders.

Alpha-Synucleinopathies

2021 ◽  
pp. 387-410
Author(s):  
Carlos Henrique Ferreira Camargo ◽  
Marcus Vinicius Della-Coletta ◽  
Delson José da Silva ◽  
Hélio A. G. Teive
Keyword(s):  
Multiple System Atrophy ◽  
Neurodegenerative Disorders ◽  
Dementia With Lewy Bodies ◽  
Therapeutic Targets ◽  
Lewy Bodies ◽  
Lysosomal Storage Diseases ◽  
Alpha Synuclein ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Abnormal Accumulation

Alpha-synuclein is a protein that forms a major component of abnormal neuronal aggregates known as Lewy bodies. A particular group of neurodegenerative disorders (NDs) is characterized by the abnormal accumulation of α-synuclein; termed the α-synucleinopathies, this group includes Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Lysosomal storage diseases have also been linked to α-synuclein toxicity. Several therapeutic targets have been chosen among steps of metabolism of α-synuclein. Reducing α-synuclein synthesis or expression and increasing the clearance can be achieved in many ways. The development of immunotherapeutic approaches targeting α-synuclein has received considerable attention in recent years. The aim of this chapter is to present the α-synucleinopathies, as well as to present the most recent researches about treatment of synucleinopathies based on knowledge of the pathophysiology of α-synuclein pathways.

Dementia and Parkinson’s disease

2020 ◽  
pp. 115-118
Author(s):  
Rodolfo Savica ◽  
Pierpaolo Turcano
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Neurodegenerative Disease ◽  
Diagnostic Criteria ◽  
Symptom Onset ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Geographic Locations ◽  
Epidemiological Characteristics

Parkinson’s disease (PD) is a neurodegenerative disease that shares a number of clinical, pathological, and epidemiological characteristics with dementing illnesses. In addition, PD and related disorders have been associated with cognitive decline/dementia. The timeline of the symptom onset as well as the clinical phenotypes are crucial to define the diseases such as dementia with Lewy bodies and Parkinson’s disease dementia. The epidemiological figures of prevalence and incidence are somewhat limited, but are influenced by diagnostic criteria, geographic locations, and methodological limitations. However, it seems that age has a major role in the increase of prevalence and incidence of PD and dementia; additionally men seem to be consistently more affected than women.

P3-158: A novel locus for autosomal dominant dementia with Lewy bodies on chromosome 2Q35-36

2006 ◽  
Vol 2 ◽  
pp. S420-S420
Author(s):  
Veerle Bogaerts ◽  
Stijn De Graeve ◽  
Sebastiaan Engelborghs ◽  
Julie van der Zee ◽  
Karin Peeters ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Autosomal Dominant ◽  
Lewy Bodies

scholarly journals Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
C. Delaby ◽  
D. Alcolea ◽  
M. Carmona-Iragui ◽  
I. Illán-Gala ◽  
E. Morenas-Rodríguez ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Lewy Bodies ◽  
Csf Biomarkers ◽  
Neurofilament Light ◽  
Cognitively Normal ◽  
Wide Range ◽  
Lateral Sclerosis ◽  
Neuroaxonal Degeneration

Abstract Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

scholarly journals Ceftriaxone Treatment for Neuronal Deficits: A Histological and MEMRI Study in a Rat Model of Dementia with Lewy Bodies

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-Jui Ho ◽  
Jun-Cheng Weng ◽  
Chih-Li Lin ◽  
Mei-Shiuan Shen ◽  
Hsin-Hua Li ◽  
...  
Keyword(s):  
Rat Model ◽  
Neurodegenerative Disorders ◽  
Dementia With Lewy Bodies ◽  
Therapeutic Agent ◽  
Lewy Bodies ◽  
Resonance Imaging ◽  
Hippocampal Ca1 ◽  
Lactam Antibiotic ◽  
Ca1 Area ◽  
The Brain

Dementia with Lewy bodies (DLB) is characterized by neuronal deficits and α-synuclein inclusions in the brain. Ceftriaxone (CEF), a β-lactam antibiotic, has been suggested as a therapeutic agent in several neurodegenerative disorders for its abilities to counteract glutamate-mediated toxicity and to block α-synuclein polymerization. By using manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemistry, we measured the effects of CEF on neuronal activity and α-synuclein accumulation in the brain in a DLB rat model. The data showed that CEF corrected neuronal density and activity in the hippocampal CA1 area, suppressed hyperactivity in the subthalamic nucleus, and reduced α-synuclein accumulation, indicating that CEF is a potential agent in the treatment of DLB.

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