Little Memories

This page exists to contain brief reports on emerging sciences related to lifestyle, genomics, disease, and therapies. These reports will not be driven toward any specific company or therapy. You should consult your physician before implementing any lifestyle or health suggestions within these reports.

Bottom-line Up Front (BLUF): According to a Linkedin post from 1 Mar 2024, Dr. Trupti P. was brought on as Associate Director of Clinical Operations at Anavex Life Science Corp. She previously worked as Clinical Project Manager for Harbor Clinical (CRO firm), the Lead Clinical Trial Manager at Icon Strategic Solutions (CRO), and Lead Clinical Trial Operations Manager at Sanofi. 

Bottom-line Up Front (BLUF): As we sleep, neurons work in synchrony to create large amplitude rhythmic waves in brain fluid which clears metabolic waste - a leading cause of numerous neurological disorders. This may help reinforce studies using light and sound therapies to target dementia. Since 2021, SOTC Analytics has assessed protein build-up/waste and neurotransmitter dysfunction to be one of - if not the - leading cause of Alzheimer's disease. Clearance of these proteins during REM sleep requires homeostatic function in the brain with particular emphasis on sleep quality, endothelial/cerebral blood flow, proper energy flow, dampened inflammation, and effective autophagy/Proteasome 26S.

Bottom-line Up Front (BLUF): It is known that mixed dementias degenerate faster than singular cause dementias. This is the case for Alzheimer's patients with a-Synuclein, a Parkinson's Disease related protein that clusters to create Lewy Bodies. It was discovered within this report that combined Alzheimer's and a-Synuclein only accelerates degeneration in mid-to-late disease stages, and that in MCI, there is no observable increase. Dr. Marwan Sabbagh is a co-author of this report, and this is the type of analysis he was brought on to the Anavex Life Sciences team for. Being a master of biomarkers and co-pathologies in mix disease Alzheimer’s, he was an excellent choice to help make sense of the Alzheimer's 2b/3 data, assess protein relationship (a-sync + tau vs a-sync + amyloid vs tau + amyloid but no a-sync, etc.), and clinical scores.

Bottom-line Up Front (BLUF): Mexico City's air is heavily polluted with heavy metals and nanoparticles. Of 57 children assayed in Mexico City, 100% had Alzheimer's pathology, or mixed dementia pathology. Endothelial, neuronal, and glial damages were extensive, as well as endoplasmic reticulum and autophagic response. Early life exposure to polluted air is a key predictor of Alzheimer's pathology and initiator of neurodegeneration. Separately, in a mouse study, mice were exposed to polluted air to assess degenerative effect. Both wild-type mice and Alzheimer's model mice were used. As a result of pollutants, the wild-type mice and Alzheimer's mice experienced neuronal loss. The Alzheimer's mice also experienced amyloid build-up. Both mice types also experiences an increase in Alzheimer's immune response and neuroinflammation. Finally, wild-type mice saw a marked increase in oxidative stress. Taken together, air quality, especially in early life, and especially in genetically prone individuals likely has lasting detrimental effects on brain development and cognition. 

Bottom-line Up Front (BLUF): In a mice study, impaired Proteasome 26S activity resulted in overt neuroinflammation in the synapse and Alzheimer's-like cognitive degeneration. Furthermore, as a result of impaired Proteasome 26S, a slew of immune-response proteins increased, including TREM2, NF-KB, and PSMC1. TREM2 is of significant interest in the clinic and trials regarding the protein are being ran for both Alector and Denali. Anavex Life Sciences has proven to restore Proteasome 26S in both Alzheimer's and Parkinson's Disease patients according to genomic analysis. 

Bottom-line Up Front (BLUF): Tau is targeted by autophagy for clearance. Fixing oxidative phosphorylation (OXPHOS) leads to enhanced autophagy and thus reduces tau. This has been shown to improve memory impairment in mice. 

Bottom-line Up Front (BLUF): Damage to the mitochondria prompts repair via the unfolded protein response (UPR). UPR jolts all parts of the mitochondria - even undamaged mitochondria elsewhere in the body - which strengthens energy circuitry and ultimately extends lifespan. The Wnt pathway is crucial to this mitochondria-to-mitochondria communication. Mitochondria of the germline proved to be especially important, and is the key regulator of organism lifespan. These studies were conducted in worms and still need to be applied to humans.