scholarly journals BACE-Inhibitors: Potential Treatment of Alzheimer Disease, Dementia, and Related Neurodegenerative Diseases. C. Spiro-Heterocyclic Derivatives

2012 ◽  
Vol 3 (11) ◽  
pp. 871-872
Author(s):  
Ahmed F. Abdel-Magid
Keyword(s):  
Alzheimer Disease ◽  
Neurodegenerative Diseases ◽  
Potential Treatment ◽  
Heterocyclic Derivatives

scholarly journals Generation and Characterization of Novel Monoclonal Antibodies Targeting p62/sequestosome-1 Across Human Neurodegenerative Diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 407-418
Author(s):  
Jorge A Trejo-Lopez ◽  
Zachary A Sorrentino ◽  
Cara J Riffe ◽  
Stefan Prokop ◽  
Dennis W Dickson ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Alzheimer Disease ◽  
Neurodegenerative Diseases ◽  
Progressive Supranuclear Palsy ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Ubiquitin Proteasome System ◽  
Lewy Neurites ◽  
Sequestosome 1 ◽  
Cellular Autophagy

Abstract Human neurodegenerative diseases can be characterized as disorders of protein aggregation. As a key player in cellular autophagy and the ubiquitin proteasome system, p62 may represent an effective immunohistochemical target, as well as mechanistic operator, across neurodegenerative proteinopathies. In this study, 2 novel mouse-derived monoclonal antibodies 5G3 and 2A5 raised against residues 360–380 of human p62/sequestosome-1 were characterized via immunohistochemical application upon human tissues derived from cases of C9orf72-expansion spectrum diseases, Alzheimer disease, progressive supranuclear palsy, Lewy body disease, and multiple system atrophy. 5G3 and 2A5 reliably highlighted neuronal dipeptide repeat, tau, and α-synuclein inclusions in a distribution similar to a polyclonal antibody to p62, phospho-tau antibodies 7F2 and AT8, and phospho-α-synuclein antibody 81A. However, antibodies 5G3 and 2A5 consistently stained less neuropil structures, such as tau neuropil threads and Lewy neurites, while 2A5 marked fewer glial inclusions in progressive supranuclear palsy. Both 5G3 and 2A5 revealed incidental astrocytic tau immunoreactivity in cases of Alzheimer disease and Lewy body disease with resolution superior to 7F2. Through their unique ability to highlight specific types of pathological deposits in neurodegenerative brain tissue, these novel monoclonal p62 antibodies may provide utility in both research and diagnostic efforts.

INECO Frontal Screening (IFS): A brief, sensitive, and specific tool to assess executive functions in dementia–CORRECTED VERSION

2009 ◽  
Vol 15 (5) ◽  
pp. 777-786 ◽  
Author(s):  
TERESA TORRALVA ◽  
MARÍA ROCA ◽  
EZEQUIEL GLEICHGERRCHT ◽  
PABLO LÓPEZ ◽  
FACUNDO MANES
Keyword(s):  
Differential Diagnosis ◽  
Alzheimer Disease ◽  
Executive Functioning ◽  
Neurodegenerative Diseases ◽  
Rating Scale ◽  
Executive Dysfunction ◽  
Screening Tools ◽  
Cognitive Screening ◽  
Clinical Dementia Rating ◽  
Per Se

AbstractAlthough several brief sensitive screening tools are available to detect cognitive dysfunction, few have been developed to quickly assess executive functioning (EF) per se. We designed a new brief tool to evaluate EF in neurodegenerative diseases. Patients with an established diagnosis of behavioral variant frontotemporal dementia (bvFTD; n = 22), Alzheimer disease (AD; n = 25), and controls (n = 26) were assessed with a cognitive screening test, the INECO Frontal Screening (IFS), and EF tests. Clinical Dementia Rating Scale (CDR) scores were obtained for all patients. Internal consistency of the IFS was very good (Cronbach’s alpha = .80). IFS total (out of 30 points) was 27.4 (SD = 1.6) for controls, 15.6 (SD = 4.2) for bvFTD, and 20.1 (SD = 4.7) for AD. Using a cutoff of 25 points, sensitivity of the IFS was 96.2%, and specificity 91.5% in differentiating controls from patients with dementia. The IFS correlated significantly with the CDR and executive tasks. The IFS total discriminated controls from demented patients, and bvFTD from AD. IFS is a brief, sensitive, and specific tool for the detection of executive dysfunction associated with neurodegenerative diseases. The IFS may be helpful in the differential diagnosis of FTD and AD. (JINS, 2009, 15, 777–786.)

scholarly journals The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration

2021 ◽  
Vol 15 ◽  
Author(s):  
Lay Khoon Too ◽  
Nicholas Hunt ◽  
Matthew P. Simunovic
Keyword(s):  
Risk Factors ◽  
Alzheimer Disease ◽  
Bacterial Meningitis ◽  
Neurodegenerative Diseases ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Similar Process ◽  
Complex Nature ◽  
Brain Functions ◽  
Age Related

Age-related neurodegenerative diseases, such as Alzheimer disease (AD) and age-related macular degeneration (AMD), are multifactorial and have diverse genetic and environmental risk factors. Despite the complex nature of the diseases, there is long-standing, and growing, evidence linking microbial infection to the development of AD dementia, which we summarize in this article. Also, we highlight emerging research findings that support a role for parainfection in the pathophysiology of AMD, a disease of the neurosensory retina that has been shown to share risk factors and pathological features with AD. Acute neurological infections, such as Bacterial Meningitis (BM), trigger inflammatory events that permanently change how the brain functions, leading to lasting cognitive impairment. Neuroinflammation likewise is a known pathological event that occurs in the early stages of chronic age-related neurodegenerative diseases AD and AMD and might be triggered as a parainfectious event. To date, at least 16 microbial pathogens have been linked to the development of AD; on the other hand, investigation of a microbe-AMD relationship is in its infancy. This mini-review article provides a synthesis of existing evidence indicating a contribution of parainfection in the aetiology of AD and of emerging findings that support a similar process in AMD. Subsequently, it describes the major immunopathological mechanisms that are common to BM and AD/AMD. Together, this evidence leads to our proposal that both AD and AMD may have an infectious aetiology that operates through a dysregulated inflammatory response, leading to deleterious outcomes. Last, it draws fresh insights from the existing literature about potential therapeutic options for BM that might alleviate neurological disruption associated with infections, and which could, by extension, be explored in the context of AD and AMD.

scholarly journals The Microbiota–Gut–Brain Axis–Heart Shunt Part II: Prosaic Foods and the Brain–Heart Connection in Alzheimer Disease

2020 ◽  
Vol 8 (4) ◽  
pp. 493 ◽  
Author(s):  
Mark Obrenovich ◽  
Shams Tabrez ◽  
Bushra Siddiqui ◽  
Benjamin McCloskey ◽  
George Perry
Keyword(s):  
Alzheimer Disease ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Vascular Dementia ◽  
Brain Aging ◽  
Polyphenolic Compounds ◽  
Heart Health ◽  
Host Liver ◽  
The Brain ◽  
French Paradox

There is a strong cerebrovascular component to brain aging, Alzheimer disease, and vascular dementia. Foods, common drugs, and the polyphenolic compounds contained in wine modulate health both directly and through the gut microbiota. This observation and novel findings centered on nutrition, biochemistry, and metabolism, as well as the newer insights we gain into the microbiota-gut-brain axis, now lead us to propose a shunt to this classic triad, which involves the heart and cerebrovascular systems. The French paradox and prosaic foods, as they relate to the microbiota-gut-brain axis and neurodegenerative diseases, are discussed in this manuscript, which is the second part of a two-part series of concept papers addressing the notion that the microbiota and host liver metabolism all play roles in brain and heart health.

1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases

2013 ◽  
Vol 21 (23) ◽  
pp. 7435-7452 ◽  
Author(s):  
Pierre Koch ◽  
Rhalid Akkari ◽  
Andreas Brunschweiger ◽  
Thomas Borrmann ◽  
Miriam Schlenk ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Potential Treatment ◽  
Multiple Target
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