Alzheimer's Research

In Alzheimer’s disease, degeneration of brain synapses happens before Beta Amyloid plaques and Tau protein aggregates are produced.

Both in AD and in its animal models the loss of neuronal plasticity is known to precede any overt formation of Aβ plaques and hyperphosphorylated (p) tau neurofibrillary tangles.” (1)

“Alzheimer’s disease responds to neurodegeneration by initiating neurogenesis in the dentate gyrus which, however, due to a lack of the proper neurotrophic support, is not sustained and the newborn neurons do not mature into functional cells.” (1)

“Alzheimer’s disease is characterized by neurodegeneration associated with loss of neuronal plasticity and in the dentate gyrus, proliferation of newborn cells which do not mature into functional neurons…” (1)

“Two major therapeutic approaches to Alzheimer’s disease and related conditions.While one therapeutic approach to Alzheimer’s disease is the inhibition of neurodegeneration that is associated with neurofibrillary and Aβ pathologies, another approach is to stimulate the regeneration of the brain by enhancing neuronal plasticity and neurogenesis that culminates into formation of mature functional neurons.” (1)

Proper neurogenesis (birth of new neurons) by peptide P021 was shown to remove Tau protein aggregates and reduce the production of new Beta Amyloid plaques.

“Moreover, the P021 treatment markedly reduced tau pathology and attenuated the generation but not the clearance of Aβ in 3xTg-AD mice.” (2)

“Cognitive performance was studied by assessing episodic memory with Novel Object Recognition task at 16-17-months post-treatment. We found that P021 treatment initiated during the synaptic compensation period can prevent neurodegeneration, Aβ and tau pathologies, rescue episodic memory impairment, and markedly reduce mortality rate. These findings for the first time show effective prevention of AD changes with a neurotrophic compound that targets neurogenesis and synaptic plasticity, suggesting that improving the health of the neuronal network can prevent AD.” (3)

“The AD brain responds to neurodegeneration by stimulating neurogenesis, however, because of the lack of a proper neurotrophic microenvironment of the hippocampus, this effort of the AD brain to replace lost neurons with new neurons is unsuccessful and culminates in failure of neuronal survival, maturation, and integration. As the disease progresses, the neurogenic failure becomes severe, and contributes significantly to cognitive decline.” (4)

Cerebrolysin and Vascular Dementia

A Look into the Research:

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD). The term ‘vascular dementia’ refers to a constellation of cognitive and functional impairments all caused by disordered blood flow to the brain. Vascular dementia can be considered a subset of the larger syndrome of vascular cognitive impairment (VCI), that is all cognitive syndromes associated with a cerebrovascular brain injury. VaD includes dementia caused by ischemic or hemorrhagic cerebrovascular diseases (CVD) or by ischemic hypoxic brain lesions of cardiovascular origin.

Vascular dementia and stroke disease are closely linked, but the terms VaD and poststroke dementia (PSD) are not synonymous. Although most PSD cases are pathologically confirmed as VaD, some have been reported to be other dementia related pathologies, such as AD.

Vascular dementia has traditionally received less attention than AD, yet international epidemiological data suggest a substantial global burden from VaD. The prevalence rate of VaD has been estimated to double every 5.3 years, compared with every 4.5 years for AD. In North America, AD accounts for 44% to 70% of all dementia, while VaD accounts for 14.5% to 20%. Studies in the UK have estimated the incidence rate of AD as 1.59/1000 person years, whilst the incidence rate of VaD was 0.99 cases/1000 person years. The prevalence of VaD among individuals aged 65 years and older was 1.50% in China between 2008 and 2009, while AD was the leading cause of dementia (3.21%). Although earlier studies in Japanese populations demonstrated a greater prevalence of VaD than AD, recent studies have shown that the trend has shifted with no changes in VaD prevalence and increases in AD prevalence over time.

Cognition is a complex system encompassing processes such as episodic memory, working memory, executive function/inhibition, spatial learning, language/vocabulary comprehension, processing speed, and language/reading decoding. Changes in synaptic plasticity, the ability of the brain to change and adapt to new information, can be short lived from milliseconds to years. Short lived forms include facilitation, augmentation, and potentiation which enhances neurotransmitter release.

These dynamic changes represent the molecular basis for learning and memory. This synaptic plasticity can be influenced by several factors e.g., aging, diseases (obesity, diabetes, hypertension, dyslipidemia), toxins (smoking and alcohol), and exercise. Aging has been estimated to trigger performance decline with an incidence of mild cognitive impairment of 21.5–71.3 per 1000 person-years). Cortical thickness and subcortical volume are shrinking 0.5–1% annually as a morphological sign of cognitive decline with plaques and axonal degeneration. Dementia is diagnosed when the acquired cognitive impairment has become severe enough to compromise social and/or occupational functioning with increasing prevalence.

Worldwide, around 50 million people have dementia and, with one new case every three seconds, the number of people with dementia is set to triple by 2050. Thus, there is a huge need for new research in order to combat the above-mentioned metrics. The peptides below have undergone extensive research to help aid in the improvement for our neurocognitive system.

Selank

Both Selank and Semax are melanocortin’s and have pleiotropic effects involved in brain health and function. Selank by itself has traditionally been prescribed for anxiety and depression. Selank has pronounced anxiolytic activity and acts as a stable neuropsychotropic, antidepressant, and anti-stress medication.

Semax

Semax is used as a therapeutic with pathologies related to brain circulation dysfunction. As a combination, Selank/Semax has applications in improving learning processes, exploratory behavior, regeneration and development, nociceptive and in amatory processes, accelerate nerve regeneration and improve neuromuscular performance and overall neural health.

SHMOOSE microprotein, a novel mitochondrial DNA variation connected to Alzheimer’s Disease pathology

Alzheimer’s is a disease that has recently caught the attention of researchers because of the alarming increase in cases through the years. ^[1,7] This rare but common disorder affects around 6.07 million people in 2020 in the United States. ^[5] Now, there is no cure for AD. ^[7] The complexity of AD pathology makes it challenging for investigators to find solutions like treatments for the disease. Even though there is no cure, three acetylcholinesterase inhibitors therapies are approved by the FDA (donepezil, galantamine, and rivastigmine). ^[7] Acetylcholinesterase inhibitors therapies help compensate death of cholinergic neurons and offer symptomatic relief by inhibiting acetylcholine (Ach) turnover and restoring synaptic levels of this neurotransmitter. ^[7] The inhibition of the cholinesterase (AChE) helps in the deficit of Ach in AD patients by avoiding the conversion of Ach to acetate and choline, thus increasing the Ach levels in the synaptic cleft (see FIGURE 1). 

NAD+ is the second most abundant cofactor in the human body. Anti-aging therapies are becoming more mainstream as aging is now more often being viewed as a disease. Now that this transition is happening, the ability for NAD+ to activate PARPS, Sirtuins, and help with immune dysregulation has been thoroughly investigated and NAD+ and its precursors have been highly popularized. The clinical importance of maintaining cellular NAD+ levels was established early in the last century with the finding that pellagra, a disease characterized by diarrhea, dermatitis, dementia and death, could be cured with foods containing the NAD+ precursor niacin.

Additionally, cellular concentrations of NAD+ have been shown to decrease under conditions of increased oxidative damage such as occur during aging Altered levels of NAD+ have been found to accompany several disorders associated with increased oxidative/free radical damage including diabetes, heart disease, age-related vascular dysfunction, ischemic brain injury, misfolded neuronal proteins, and Alzheimer’s dementia. Interventions targeted at restoring NAD+ has been shown in animal models to support healthy aging and improve metabolic function, and dementia.

A need for NAD+ in muscle development, homeostasis, and aging

In a review study, researchers discuss the recent data that document conserved roles for NAD+ in skeletal muscle development, regeneration, aging, and disease as well as interventions targeting skeletal muscle and affecting NAD+ that suggest promising therapeutic benefits. The researchers also highlight gaps in our knowledge and propose avenues of future investigation to better understand why and how NAD+ regulates skeletal muscle biology.