SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Alois Alzheimer

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In recent years consumption of canola oil has increased due to lower cost compared with olive oil and the perception that it shares its health benefits. However, no data are available on the effect of canola oil intake on Alzheimer’s disease (AD) pathogenesis. Herein, we investigated the effect of chronic daily consumption of canola oil on the phenotype of a mouse model of AD that develops both plaques and tangles (3xTg). To this end mice received either regular chow or a chow diet supplemented with canola oil for 6 months. At this time point we found that chronic exposure to the canola-rich diet resulted in a significant increase in body weight and impairments in their working memory together with decrease levels of post-synaptic density protein-95, a marker of synaptic integrity, and an increase in the ratio of insoluble Aβ 42/40. No significant changes were observed in tau phosphorylation and neuroinflammation. Taken together, our findings do not support a beneficial effect of chronic canola oil consumption on two important aspects of AD pathophysiology which includes memory impairments as well as synaptic integrity. While more studies are needed, our data do not justify the current trend aimed at replacing olive oil with canola oil.

Concepts: Alzheimer's disease, Neuron, Fatty acid, Neurology, Ratio, Semantic memory, Tau protein, Alois Alzheimer

28

Ligands of the translocator protein (TSPO) elicit pleiotropic neuroprotective effects that represent emerging treatment strategies for several neurodegenerative conditions. To investigate the potential of TSPO as a therapeutic target for Alzheimer’s disease (AD), the current study assessed the effects of the TSPO ligand Ro5-4864 on the development of neuropathology in 3xTgAD mice. The effects of the TSPO ligand on neurosteroidogenesis and AD-related neuropathology, including β-amyloid accumulation, gliosis, and behavioral impairment, were examined under both early intervention (7-month-old young-adult male mice with low pathology) and treatment (24-month-old, aged male mice with advanced neuropathology) conditions. Ro5-4864 treatment not only effectively attenuated development of neuropathology and behavioral impairment in young-adult mice but also reversed these indices in aged 3xTgAD mice. Reduced levels of soluble β-amyloid were also observed by the combination of TSPO ligands Ro5-4864 and PK11195 in nontransgenic mice. These findings suggest that TSPO is a promising target for the development of pleiotropic treatment strategies for the management of AD.

Concepts: Alzheimer's disease, Positron emission tomography, Peptide, Neurology, Neurodegenerative disorders, Mice, Neuropathology, Alois Alzheimer

28

This review aims to address the temporal sequencing of involvement of amyloid-beta (Aβ) and tau in the pathogenesis of Alzheimer’s disease and reconcile apparently conflicting neuropathologic and biomarker data.

Concepts: Alzheimer's disease, Neurology, Beta amyloid, Apomorphine, Neuropathology, Alois Alzheimer, Proteopathy

8

To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD.

Concepts: Alzheimer's disease, Medicine, Genetics, Clinical trial, Neuropathology, Alois Alzheimer, Aphasias

6

Abstract: To assess the ability of a traditional Chinese medicinal ginger root extract (GRE) to prevent behavioural dysfunction in the Alzheimer’s disease rat model. Rat AD models were established by an operation (OP) in which rats were treated with one-time intracerebroventricuIar injection of amyloid β-protein (Aβ) and continuous gavage of aluminum chloride every day for 4 weeks. GRE was administered intragastrically to rats. After 35 days, learning and memory was assessed in all of the rats. Brain sections were processed for immunohistochemistry, hematoxylin-eosin (H.E.) and Nissl staining. The latency to show significant memory deficits was shorter in the group that received OP with a high dose of GRE (HG)(OP + HG) than in the groups that received OP with a low or moderate dose of GRE (LG, MG)(OP + LG, OP + MG)(P < 0.05). The expression of superoxide dismutase (SOD) and catalase (CAT) in the OP + MG and OP + LG groups was upregulated compared to the OP + HG groups (P < 0.05). The rats in the OP + HG groups had lower levels of nuclear factor Kb (NF-kB), interleukin-1β (IL-1β) and malondialdehyde (MDA) expression than the rats in the OP + MG and OP + LG groups (P < 0.05). This experiment demonstrates that the administration of GRE reverses behavioural dysfunction and prevents Alzheimer's disease-like symptoms in our rat model. Key words: ginger root extract (GRE); Alzheimer's disease (AD); amyloid β-protein (Aβ); behaviour dysfunction; metabolic factors.

Concepts: Alzheimer's disease, Superoxide dismutase, Memory, Aluminium, Beta amyloid, Alois Alzheimer, Turmeric, Franz Nissl

5

Obesity and insulin resistance are associated with neuropathology and cognitive decline in Alzheimer’s disease (AD).

Concepts: Alzheimer's disease, Insulin, Diabetes mellitus, Obesity, Insulin resistance, Metabolic syndrome, Neuropathology, Alois Alzheimer

5

Bapineuzumab is a humanized antibody developed by Pfizer and Johnson & Johnson targeting the amyloid (Aβ) plaques that underlie Alzheimer’s disease neuropathology. Here we report the crystal structure of a Fab-Aβ peptide complex that reveals Bapineuzumab surprisingly captures Aβ in a monomeric helical conformation at the N-terminus. Microscale thermophoresis suggests that the Fab binds soluble Aβ(1-40) with a K(D) of 89 (±9) nM. The structure explains the antibody’s exquisite selectivity for particular Aβ species and why it cannot recognize N-terminally modified or truncated Aβ peptides.

Concepts: Alzheimer's disease, Protein, Mitochondrion, Peptide, Beta amyloid, Neuropathology, Alois Alzheimer, Bapineuzumab

4

Down syndrome (DS) shows neuropathology similar to Alzheimer disease, which presents olfactory impairment. Previous work showed olfactory impairment in DS, but a comprehensive evaluation of olfactory function in DS is lacking.

Concepts: Alzheimer's disease, Neurology, Olfaction, Down syndrome, Neuropathology, Alois Alzheimer

3

The 12/15-lipoxygenase (12/15-LO) enzyme is upregulated in the brains of patients with Alzheimer’s disease (AD), and its expression levels influence the onset of the AD-like phenotype in mouse models. However, whether targeting this pathway after the neuropathology and behavioral impairments have been established remains to be investigated.

Concepts: Alzheimer's disease, Gene, Gene expression, Brain, Molecular biology, Neurology, Genetically modified organism, Alois Alzheimer

3

Given the complex neuropathology Alzheimer’s disease (AD), combination therapy may be necessary for effective treatment. However, scientific, pragmatic, regulatory, and business challenges need to be addressed before combination therapy for AD can become a reality. Leaders from academia and industry, along with a former member of the Food and Drug Administration and the Alzheimer’s Association, have explored these challenges and here propose a strategy to facilitate proof-of-concept combination therapy trials in the near future. First, a more integrated understanding of the complex pathophysiology and progression of AD is needed to identify the appropriate pathways and the disease stage to target. Once drug candidates are identified, novel clinical trial designs and selection of appropriate outcome assessments will be needed to enable definition and evaluation of the appropriate dose and dosing regimen and determination of efficacy. Success in addressing this urgent problem will only be achieved through collaboration among multiple stakeholders.

Concepts: Alzheimer's disease, Clinical trial, Effectiveness, Wandering, Neuropathology, Alois Alzheimer, Rita Hayworth, Alzheimer's Association