Therapeutics of Alzheimer’s Disease: Recent Developments

Burns, Scott; Sehar, Ujala; Rawat, Priyanka; Reddy, Arubala P.; Reddy, P. Hemachandra

doi:10.3390/antiox11122402

Cited by 15 publications

(13 citation statements)

References 144 publications

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“…Indeed, treatments with antioxidant properties have also been shown to improve memory in rodent models of AD including the SAMP8 mouse (42)(43)(44). However, the results of trials of antioxidants such as Vitamin E (α-tocopherol), C and ubiquinone (CoQ10) as therapies for AD have been disappointing, perhaps due to the large amounts of these antioxidants that are needed to reach effective levels in brain tissue (45,46).…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 Mice

Goodland,

Banerjee,

Niehoff

et al. 2023

Preprint

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Cannabidiol (CBD) has gained a lot of interest in recent years for its purported medicinal properties. CBD has been investigated for the treatment of anxiety, depression, epilepsy, neuroinflammation, and pain. Recently there has been an interest in CBD as a possible treatment for age-related disorders such as Alzheimer’s disease and related disorders (ADRD). Here we tested the hypothesis that chronic CBD administration would improve learning and memory in the SAMP8 mouse model of Alzheimer’s disease. SAMP8 mice aged 11 months (at the start of the study) were administered vehicle or CBD (3 or 30 mg/Kg) daily via oral gavage for 2 months. Vehicle-treated young SAMP8 mice (age 3 months at the start of the study) served as unimpaired controls. After 30 days of treatment (4 and 12 months of age), learning and memory, activity, anxiety, strength and dexterity were assessed. High dose CBD treatment significantly improved learning and memory of the 12-month-old mice in the T maze. Novel object recognition memory was also improved by CBD in aged CBD treated mice. Aged CBD treated mice also displayed less anxiety in the elevated plus maze test compared to controls. However, activity and strength levels were similar between groups. Biochemical analysis revealed decreased markers of oxidative stress, providing a possible mechanism by which CBD treatment impacts learning, memory, and anxiety. These results highlight the potential use of CBD as a therapeutic for age related cognitive impairment and dementia.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 Mice

Goodland,

Banerjee,

Niehoff

et al. 2023

Preprint

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“…Vascular dementia is characterized as dementia that affects the brain’s blood supply. Numerous clinical issues (such as stroke) or ischemic brain damage to the white matter fibers in the brain might result from these blood vessel anomalies [ 43 ]. Early signs of different types of dementia can occasionally be difficult to diagnose as they can be vague and misleading.…”

Section: Alzheimer’s Disease and Alzheimer’s Disease Related Dementiasmentioning

confidence: 99%

Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias in African Americans: Focus on Caregivers

et al. 2023

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Alzheimer’s disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are chronic illnesses that are highly prevalent in African Americans (AA). AD and ADRD are caused by multiple factors, such as genetic mutations, modifiable and non-modifiable risk factors, and lifestyle. Histopathological, morphological, and cellular studies revealed how multiple cellular changes are implicated in AD and ADRD, including synaptic damage, inflammatory responses, hormonal imbalance, mitochondrial abnormalities, and neuronal loss, in addition to the accumulation of amyloid beta and phosphorylated tau in the brain. The contributions of race, ethnicity, location and socioeconomic status all have a significant impact on the care and support services available to dementia patients. Furthermore, disparities in health care are entangled with social, economic, and environmental variables that perpetuate disadvantages among different groups, particularly African Americans. As such, it remains important to understand how various racial and ethnic groups perceive, access, and experience health care. Considering that the mounting data shows AA may be more susceptible to AD than white people, the demographic transition creates significant hurdles in providing adequate care from family caregivers. Furthermore, there is growing recognition that AD and ADRD pose a significant stress on AA caregivers compared to white people. In this review, we examine the current literature on racial disparities in AD and ADRD, particularly concerning AA caregivers.

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“…Our search did not have to go far to find limited success that has the potential to be linked to the above model. Methylene blue (MB) is (1) the oldest synthetic dye, (2) usable in humans up to about 2 mg/kg body weight and (3) a limited AD suppressor in both humans and animals [ 51 , 52 , 53 ]. The AD suppression is thought to originate primarily via the enhancement of respiration in mitochondria [ 52 ], an effect that MB has been shown to have [ 54 ].…”

Section: Introduction: Previous Data and Our Best-fit Modelmentioning

confidence: 99%

“…Methylene blue (MB) is (1) the oldest synthetic dye, (2) usable in humans up to about 2 mg/kg body weight and (3) a limited AD suppressor in both humans and animals [ 51 , 52 , 53 ]. The AD suppression is thought to originate primarily via the enhancement of respiration in mitochondria [ 52 ], an effect that MB has been shown to have [ 54 ]. However, also possible is that MB binds and detoxifies the toxic conformation of amyloid-forming proteins.…”

Section: Introduction: Previous Data and Our Best-fit Modelmentioning

confidence: 99%

Alzheimer’s Disease: A Molecular Model and Implied Path to Improved Therapy

Weaver-Rosen,

Serwer

2024

IJMS

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Amyloid-associated neurodegenerative diseases, including Alzheimer’s disease (AD), are characterized by the in-brain accumulation of β-sheet structured protein aggregates called amyloids. However, neither a disease model nor therapy is established. We review past data and present new, preliminary data and opinions to help solve this problem. The following is the data-derived model/hypothesis. (1) Amyloid-forming proteins have innate immunity functions implemented by conversion to another sheet conformation, α-sheet. (2) In health, α-sheet structured, amyloid-forming proteins inactivate microbes by co-assembly with microbe α-sheets. Amyloid-forming proteins then undergo α-to-β-sheet conversion. (3) In disease, α-sheet-structured, amyloid-forming proteins over-accumulate and are neuron-toxic. This hypothesis includes formation by virus capsid subunits of α-sheets. In support, we find that 5–10 mM methylene blue (MB) at 54 °C has a hyper-expanding, thinning effect on the phage T4 capsid, as seen by negative stain- and cryo-electron microscopy after initial detection by native gel electrophoresis (AGE). Given the reported mild anti-AD effect of MB, we propose the following corollary hypothesis. (1) Anti-AD MB activity is, at least in part, caused by MB-binding to amyloid α-sheet and (2) MB induces the transition to α-sheet of T4 capsid subunits. We propose using AGE of drug incubated T4 to test for improved anti-AD activity.

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Therapeutics of Alzheimer’s Disease: Recent Developments

Cited by 15 publications

References 144 publications

Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 Mice

Cannabidiol improves learning and memory deficits and alleviates anxiety in 12-month-old SAMP8 Mice

Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias in African Americans: Focus on Caregivers

Alzheimer’s Disease: A Molecular Model and Implied Path to Improved Therapy

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