New Insights into the Spontaneous Human Alzheimer’s Disease-Like Model Octodon degus: Unraveling Amyloid-β Peptide Aggregation and Age-Related Amyloid Pathology

2018 ◽  
Vol 66 (3) ◽  
pp. 1145-1163 ◽  
Author(s):  
Pedro Cisternas ◽  
Juan M. Zolezzi ◽  
Carolina Lindsay ◽  
Daniela S. Rivera ◽  
Alexis Martinez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Peptide Aggregation ◽  
Octodon Degus ◽  
Amyloid Pathology ◽  
Age Related

scholarly journals Amyloid-β dimers in the absence of plaque pathology impair learning and synaptic plasticity

Brain ◽  
2015 ◽  
Vol 139 (2) ◽  
pp. 509-525 ◽  
Author(s):  
Andreas Müller-Schiffmann ◽  
Arne Herring ◽  
Laila Abdel-Hafiz ◽  
Aisa N. Chepkova ◽  
Sandra Schäble ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Biological Effects ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Amyloid Β Peptide ◽  
Age Related ◽  
Plaque Pathology

Abstract Despite amyloid plaques, consisting of insoluble, aggregated amyloid-β peptides, being a defining feature of Alzheimer’s disease, their significance has been challenged due to controversial findings regarding the correlation of cognitive impairment in Alzheimer’s disease with plaque load. The amyloid cascade hypothesis defines soluble amyloid-β oligomers, consisting of multiple amyloid-β monomers, as precursors of insoluble amyloid-β plaques. Dissecting the biological effects of single amyloid-β oligomers, for example of amyloid-β dimers, an abundant amyloid-β oligomer associated with clinical progression of Alzheimer’s disease, has been difficult due to the inability to control the kinetics of amyloid-β multimerization. For investigating the biological effects of amyloid-β dimers, we stabilized amyloid-β dimers by an intermolecular disulphide bridge via a cysteine mutation in the amyloid-β peptide (Aβ-S8C) of the amyloid precursor protein. This construct was expressed as a recombinant protein in cells and in a novel transgenic mouse, termed tgDimer mouse. This mouse formed constant levels of highly synaptotoxic soluble amyloid-β dimers, but not monomers, amyloid-β plaques or insoluble amyloid-β during its lifespan. Accordingly, neither signs of neuroinflammation, tau hyperphosphorylation or cell death were observed. Nevertheless, these tgDimer mice did exhibit deficits in hippocampal long-term potentiation and age-related impairments in learning and memory, similar to what was observed in classical Alzheimer’s disease mouse models. Although the amyloid-β dimers were unable to initiate the formation of insoluble amyloid-β aggregates in tgDimer mice, after crossbreeding tgDimer mice with the CRND8 mouse, an amyloid-β plaque generating mouse model, Aβ-S8C dimers were sequestered into amyloid-β plaques, suggesting that amyloid-β plaques incorporate neurotoxic amyloid-β dimers that by themselves are unable to self-assemble. Our results suggest that within the fine interplay between different amyloid-β species, amyloid-β dimer neurotoxic signalling, in the absence of amyloid-β plaque pathology, may be involved in causing early deficits in synaptic plasticity, learning and memory that accompany Alzheimer’s disease. 10.1093/brain/awv355_video_abstract awv355_video_abstract

scholarly journals Biochemical stages of amyloid-β peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically preclinical Alzheimer’s disease

Brain ◽  
2014 ◽  
Vol 137 (3) ◽  
pp. 887-903 ◽  
Author(s):  
Ajeet Rijal Upadhaya ◽  
Irina Kosterin ◽  
Sathish Kumar ◽  
Christine A. F. von Arnim ◽  
Haruyasu Yamaguchi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Peptide Aggregation ◽  
Preclinical Alzheimer’S Disease

scholarly journals Immunotherapeutic Strategies for Alzheimer's Disease Treatment

2009 ◽  
Vol 9 ◽  
pp. 909-919 ◽  
Author(s):  
Beka Solomon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Passive Immunization ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Treatment ◽  
Naturally Occurring ◽  
Age Related ◽  
The Central Nervous System ◽  
Naturally Occurring Antibodies

Naturally occurring antibodies against amyloid-β peptides have been found in human cerebrospinal fluid and in the plasma of healthy individuals, but were significantly lower in Alzheimer's disease (AD) patients, suggesting that AD may be an immunodeficient disorder. The performance of anti-amyloid-β antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system, preventing and dissolving amyloid-β plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Active and/or passive immunization against the amyloid-β peptide has been proposed as a method for preventing and/or treating AD. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.

scholarly journals Posttranslational Nitro-Glycative Modifications of Albumin in Alzheimer's Disease: Implications in Cytotoxicity and Amyloid-β Peptide Aggregation

2014 ◽  
Vol 40 (3) ◽  
pp. 643-657 ◽  
Author(s):  
Eva Ramos-Fernández ◽  
Marta Tajes ◽  
Ernest Palomer ◽  
Gerard ILL-Raga ◽  
Mònica Bosch-Morató ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Peptide Aggregation

Recent advances in the design and applications of amyloid-β peptide aggregation inhibitors for Alzheimer’s disease therapy

2019 ◽  
Vol 11 (6) ◽  
pp. 901-925 ◽  
Author(s):  
Safura Jokar ◽  
Saeedeh Khazaei ◽  
Hossein Behnammanesh ◽  
Amir Shamloo ◽  
Mostafa Erfani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Peptide Aggregation ◽  
Recent Advances ◽  
Disease Therapy ◽  
Aggregation Inhibitors
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