Effects of GrandFusion Diet on Cognitive Impairment in Transgenic Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the result of the deposition of amyloid β (Aβ) peptide into amyloid fibrils and tau into neurofibrillary tangles. At the present time, there are no possible treatments for the disease. We have recently shown that diets enriched in phytonutrients show protection or limit the extent of damage in a number of neurological disorders. GrandFusion (GF) diets have attenuated the outcomes in animal models of traumatic brain injury, cerebral ischemia, and chronic traumatic encephalopathy. In this study, we investigated the effect of GF diets in a mouse model of AD prior to the development of amyloid plaques to show how this treatment paradigm would alter the accumulation of Aβ peptide and related pathologic changes (i.e., inflammation, cathepsin B, and memory impairment). Administration of GF diets (2–4%) over a period of four months in APP/ΔPS1 double-transgenic mice resulted in attenuation in Aβ peptide levels, reduction of amyloid load, and inflammation, increased cathepsin B expression, and improved spatial orientation. Additionally, treatment with GF diets increased nerve growth factor (NGF) levels in the brain and tempered the memory impairment in the animal model. These data suggest that GF diets may alter the development and progression of the mechanisms associated with the disease process to effectively modify AD pathogenesis.

Experimental approaches for altering the expression of Abeta‐degrading enzymes

“…Experimental approaches have included both increasing and reducing of CAT‐B activity. Increasing of CAT‐B activity has been accomplished by overexpression of CAT‐B (Embury et al, 2017; Wang, Sun, et al, 2012), genetic ablation of cystatin C (Sun et al, 2008), deletion of cystatin B (which, like cystatin C, is an inhibitor of lysosomal cysteine proteases) (Yang et al, 2011), administration of a 6‐amino acid component of motoneuronotrophic factor, an endogenous neurotrophin (Yu et al, 2019), and feeding a phytonutrient‐enriched diet (Yu et al, 2020). Reducing of CAT‐B activity has been accomplished by administration of the selective cathepsin‐B inhibitor CA‐074 (Hook et al, 2008), knockout of CAT‐B (Hook et al, 2009), administration of the phosphodiesterase‐5 inhibitor Sildenafil (Orejana et al, 2015), treatment with bilobalide, a Ginkgo biloba extract (Shi et al, 2012), and treatment with E64d, a cysteine protease inhibitor of CAT‐B (Hook et al, 2014).…”

A Novel polysaccharide DSPP-1 from Durian seed: structure characterization and its neuroprotective effects against Alzheimer's disease in a transgenic Caenorhabditis elegans model

“…Aβ readily self-assembles into amyloid brils, which are the major components of the amyloid plaques that represent molecular hallmark of AD (Quartey et al, 2021). Aβ 1−40 and Aβ 1−42 are the two most abundant forms of Aβ in the brain (Yu et al, 2021). Moreover, Aβ 1−42 readily forms aggregates and has higher neurotoxicity than Aβ 1−40 (Zhang et al, 2021).…”

Novel Positron Emission Tomography Radiotracers for Imaging Mitochondrial Complex I

“…Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive functions. Approximately, 1 in 10 individuals over the age of 65 suffers from AD, a figure set to increase to 1 in 3 over the age of 85 . Although numerous studies have been dedicated to understanding the mechanisms leading to AD, − the exact etiology of AD remains elusive.…”