FunGen-AD-funded research reveals cellular pathways in Alzheimer’s development and brain aging

A research team including FunGen-AD researcher Philip De Jager used data from 1.6 million brain cells to characterize the cellular changes associated with Alzheimer’s disease (AD). The analysis used over 400 brains from the Religious Orders Study and the Memory & Aging Project based at Rush University in Chicago. These brains were from healthy donors or people at different stages of AD progression. Single-cell RNA sequencing data from cells extracted from the prefrontal cortex were analyzed using algorithms and machine-learning techniques.

Based on the sequencing results, microglia were categorized into 16 different populations, and astrocytes were categorized into 10 distinct populations. The research team used a custom-designed algorithm called BEYOND to identify two distinct trajectories for aging brains: normal aging and increased toxic protein buildup that led to AD dementia. In the AD dementia path, two distinct microglial populations start the process of amyloid or tau accumulation, respectively. Following this protein accumulation, astrocytes play a role in altering electrical connectivity in the brain that leads to cognitive impairment. Interestingly, the algorithm predicted that astrocytes may be a “point of convergence” for processes that lead to normal brain aging or dementia. This study provides insights on how individual cells contribute to AD development and progression and could lead to therapies targeting specific cell groups involved in AD.

This research, partially supported by FunGen-AD grant U01AG072572, is published in Nature here. You can read more about these research findings at the following links: