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Drug Development.

Alzheimers Dement

December 2024

Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.

Background: The vicious cycle between depression and dementia increases the risk of Alzheimer's Disease (AD) pathogenesis and pathology. This study investigates therapeutic effectiveness versus side effects and the underlying mechanisms of intranasal dantrolene nanoparticles (IDNs) to treat depression behavior and memory loss in 5XFAD mice.

Method: 5XFAD and wild-type B6SJLF1/J mice were treated with IDNs (IDN, 5 mg/kg) in Ryanodex formulation for a duration of 12 weeks.

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Drug Development.

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December 2024

Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China;, Beijing, China.

Background: Individuals with type 2 diabetes mellitus (T2DM) face an increased risk of dementia. Recent discoveries indicate that SGLT2 inhibitors, a newer class of anti-diabetic medication, exhibit beneficial metabolic effects beyond glucose control, offering a potential avenue for mitigating the risk of Alzheimer's disease (AD). However, limited evidence exists regarding whether the use of SGLT2 inhibitors effectively reduces the risk of AD.

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Drug Development.

Alzheimers Dement

December 2024

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Anti-amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti-amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer.

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Background: Homozygosity for the rare APOE3-Christchurch (APOE3Ch) variant, encoding for apoE3-R136S (apoE3-Ch), was linked to resistance against an aggressive form of familial Alzheimer's disease (AD). Carrying two copies of APOE3Ch was sufficient to delay autosomal AD onset by 30 years. This remarkable protective effect makes it a strong candidate for uncovering new therapies against AD.

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Background: Dementia, a growing health crisis, disproportionally affects persons from racial/ethnic backgrounds and individuals with comorbidities. Latelife change in cognition is complex and nonlinear, as well as differential for these individuals. These individuals are also largely underrepresented in clinical trials.

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