Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease

Abstract Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.

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(-)-Oleocanthal Nutraceuticals for Alzheimer’s Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model

Nutrients ◽

10.3390/nu13051702 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1702

Author(s):

Afsana Tajmim ◽

Areli K. Cuevas-Ocampo ◽

Abu Bakar Siddique ◽

Mohammed H. Qusa ◽

Judy Ann King ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Virgin Olive Oil ◽

Therapeutic Effects ◽

Dissolution Profile ◽

Amyloid Pathology ◽

Oral Formulations ◽

Aβ Amyloid ◽

Anti Inflammatory ◽

The Brain

Alzheimer’s disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aβ-amyloid (Aβ) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(–)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of β-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (SEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aβ plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.

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Amyloid β-peptide and Alzheimer's disease

Essays in Biochemistry ◽

10.1042/bse0560099 ◽

2014 ◽

Vol 56 ◽

pp. 99-110 ◽

Cited By ~ 15

Author(s):

David Allsop ◽

Jennifer Mayes

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaques ◽

Strong Support ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Amyloid Cascade Hypothesis ◽

Sequence Of Events ◽

Aβ Amyloid ◽

Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

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Faculty Opinions recommendation of Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727137776.793531343 ◽

2017 ◽

Author(s):

John Lazo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Interleukin 2 ◽

Amyloid Pathology ◽

Synaptic Failure

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Activation of CREB‐mediated autophagy by thioperamide ameliorates β‐amyloid pathology and cognition in Alzheimer’s disease

Aging Cell ◽

10.1111/acel.13333 ◽

2021 ◽

Vol 20 (3) ◽

Author(s):

Jiangong Wang ◽

Bin Liu ◽

Yong Xu ◽

Meizi Yang ◽

Chaoyun Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Pathology ◽

Β Amyloid

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NMR structure of the water soluble Aβ17–34 peptide

Bioscience Reports ◽

10.1042/bsr20140094 ◽

2014 ◽

Vol 34 (6) ◽

Cited By ~ 3

Author(s):

Genadiy Fonar ◽

Abraham O. Samson

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nicotinic Acetylcholine Receptors ◽

Neurodegenerative Disorder ◽

Amyloid Β ◽

Helical Structure ◽

Nmr Structure ◽

Water Soluble ◽

Helical Conformation ◽

Aβ Amyloid

Alzheimer's disease is the most common neurodegenerative disorder in the world. Its most significant symptoms are memory loss and decrease in cognition. Alzheimer's disease is characterized by aggregation of two proteins in the brain namely Aβ (amyloid β) and tau. Recent evidence suggests that the interaction of soluble Aβ with nAChR (nicotinic acetylcholine receptors) contributes to disease progression. In this study, we determine the NMR structure of an Aβ17–34 peptide solubilized by the addition of two glutamic acids at each terminus. Our results indicate that the Aβ peptide adopts an α-helical structure for residues 19–26 and 28–33. The α-helical structure is broken around residues S26, N27 and K28, which form a kink in the helical conformation. This α-helix was not described earlier in an aqueous solution without organic solvents, and at physiological conditions (pH 7). These data are in agreement with Aβ adopting an α-helical conformation in the membrane before polymerizing into amyloid β-sheets and provide insight into the intermediate state of Aβ in Alzheimer's disease.

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