Alzheimer’s Disease: A Decreased Cerebral Blood Flow to Critical Intraneuronal Elements is the Cause

Normally, an adequate cerebral blood flow arrives at individual cerebral neurons in which the blood flow augments activity of intraneuronal mitochondria, which is the source of intraneuronal ATP, the energy source of cerebral neurons. With a decrease in cerebral blood flow that can occur as a function of normal aging phenomena, less blood results in decreased mitochondria, decreased ATP, and a decrease in neuronal activity, which can eventually lead to Alzheimer’s disease. It has been found that placement of the omentum directly on an Alzheimer’s disease brain can lead to improved cognitive function.

Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging

Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between aging and LOAD. We found that shared gene expression changes between aging and LOAD are mostly seen in the hippocampal and several cortical regions. In the hippocampus, the expression of phosphoprotein, alternative splicing and cytoskeleton genes are commonly changed in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are more related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also found that normal aging brain transcriptomes from relatively young donors (45–70 years old) clustered into several subgroups and some subgroups showed gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptomic datasets from another cohort of older individuals (>70 years), we found that samples from cognitively normal older individuals clustered with the “healthy aging” subgroup while AD samples mainly clustered with the “AD similar” subgroups. This may imply that individuals in the healthy aging subgroup will likely remain cognitively normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitively normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the “normal brain aging” to identify the very early molecular events that may lead to LOAD development.

Irving S. Wright Award: Cellular recycling in aging and disease: The importance of taking out the trash

Aging is greatly influenced by quality-control processes that keep the materials inside our cells in proper shape and function. One of these processes is called autophagy, which means "self-eating". This cellular recycling process can digest damaged components to provide new and better parts for the cell. Autophagy plays important roles in many age-related diseases and has been directly linked to aging. In our laboratory, we use the microscopic soil-dwelling round worm C. elegans to understand how autophagy is linked to aging and disease. In this Wright Award seminar, I will discuss our progress on understanding how autophagy is regulated during normal aging and how it may promote a long and healthy lifespan.

A Comprehensive Cognitive Health Management Model for Community-Dwelling Older Adults in Shanghai

To investigate whether a comprehensive cognitive health management model improves cognitive function among community-dwelling older adults in Shanghai, China. The comprehensive cognitive health management model included brain health screening, individualized brain health consultation and referrals, and annual follow-up monitoring. We compared 161 older adults (43 with MCI, 118 with normal aging) who received the health management model, to an equal size of control group who did not receive the model on their cognition and emotion using Montreal Cognitive Assessment Scale (MoCA) and Geriatric Depression Scale (GDS). Over one-year, participants with MCI in the intervention group showed a significant increase of MoCA score than their MCI counterparts in the control group. Participants with normal aging in the intervention group showed no differences in MoCA and GDS with those in the control group. The individualized cognitive health management model is promising to assist community-dwelling older adults with MCI to maintain brain health.