Alzheimer's Disease INSIGHTS

As Alzheimer's Disease Awareness Month concludes we review the state of Alzheimer's disease (AD) research, its biological mechanisms, and available in vivo research models of AD. Alzheimer's Disease Overview Since the original National Alzheimer's Disease Awareness Month in November 1983, the number of afflicted patients in the US has risen from two to five million; it is projected to increase to 14 million by 20501. AD is...

In a recent Alzheimer's Research and Therapy article, scientists described failing to elicit beneficial effects from a tau-directed antibody therapy while evaluating its efficacy in the Tg4510 mouse, an Alzheimer's disease (AD) model with a tamoxifen-controlled transgene expressing P301L mutant tau. The results contrast prior successes reported with the antibody therapy the researchers were testing. The therapeutic, a tau oligomer-specific monoclonal antibody (TOMA), was reported to rescue...

A Redox Link between APOE4 and Alzheimer's Disease Risk? Individuals homozygous for APOE4, one of three common genetic variants encoding Apolipoprotein E (apoE), carry approximately twelve-times higher risk for an Alzheimer's disease (AD) diagnosis. A recent study suggests a potentially critical link between apoE4 and the antioxidant enzyme Thioredoxin-1 (Trx1) may underlie enhanced AD risk in APOE4 carriers. APOE Alleles Modify Alzheimer's Risk ApoE protein is predominantly...

More than 5.5 million Americans are living with Alzheimer's disease (AD), the sixth leading cause of death among adults in the US. Aggressive research funding and improved animal models of Alzheimer's disease are urgent priorities. Increasing Alzheimer's Research Funding On July 19, 2017, the House Appropriations Committee approved an additional $400 million for Alzheimer's disease research in the fiscal year 2018 budget. $400 million was also approved...

In late 2016 Biogen reported exciting results for aducanumab, their Phase 1 monoclonal antibody therapy for Alzheimer's disease (AD). Patients who received aducanumab showed significant and dose-dependent reduction of brain Amyloid-β (Aβ) and slowing of disease progression. Pre-clinical studies in the APPSWE/Tg2576 mouse model of AD provided the mechanistic clues, dosing insights, and efficacy data that informed the design of Biogen's successful aducanumab Phase I trial. Now,...

Despite tau proteins having essential roles in neurodegeneration and amyloid-mediated neurotoxicity, Alzheimer's disease (AD) therapeutic development has largely focused on amyloid-beta. Recent investigations, in humans and rodent Alzheimer's Disease models, suggest specific tau species might be major pathological contributors to AD progression and, as such, an even better target than amyloid-beta for effective AD therapies. Tau Proteins in Alzheimer's Disease Monomeric tau proteins are abundant in neurons,...

Increasingly obesity and its associated comorbidities (cardiovascular disease, type 2 diabetes mellitus, hypertension, etc.) are identified as risk factors for Alzheimer's disease (AD). Determining the link between diet and Alzheimer's disease has been challenging, in large part due to obesity's association with numerous systemic physiological changes. Recent studies suggest that poor maternal diet can influence epigenetic changes which predispose offspring to the development of metabolic syndromes. Since...

Researchers at Biogen published a pivotal Phase 1b clinical study of an Alzheimer's treatment showing not only a decrease in plaques when the monoclonal antibody aducanumab is administered, but also some cognitive improvement in humans. From the paper: "Antibody-based immunotherapy against Αβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that...

In a 2015 report, a team of scientist from the Weizmann Institute of Science provided compelling evidence that boosting the immune response in the brain (as opposed to suppressing it) might be a promising avenue for Alzheimer's research. In an extension of its initial findings, the team found that inhibiting an immune-checkpoint pathway which is targeted in the treatment of certain forms of cancer dramatically reduces Alzheimer's...

The majority of the drugs approved by the FDA for treatment of cognitive symptoms in Alzheimer's disease (AD) patients are cholinesterase inhibitors and include drugs such as donepezil, galantamine, and rivastagimine. However, the tolerated doses of cholinesterase inhibitors, such as donepezil, produce only partial improvement in memory and can have severe GI side effects. Since these medications have to be taken for prolonged durations, the limited efficacy...