The Aged Brain and Dementia

By Jane Farrell

Researchers working with aged human brains have discovered details that will help experts better understand the biological bases for Alzheimer’s and other dementias.

The analysis, from the Allen Institute for Brain Science, University of Washington Medicine and Kaiser Permanente Washington Health Research Institute, was published in the journal eLife. The investigation also highlights surprising variability in the aged brain.

“Since the population of individuals over 90 years of age is rapidly increasing, understanding both healthy aging and age-related disease is essential,” said Ed Lein, Investigator at the Allen Institute for Brain Science. “This means we must discover how cognitive decline correlates with the brain pathologies we typically attribute to diseases like Alzheimer’s in aged brains, as well as the biology underlying individual vulnerability and resilience to disease.”

In this analysis, researchers sought to understand whether associations previously identified between cognitive status, gene expression and brain pathologies–such as the plaques and tangles typically found in Alzheimer’s disease–held true in a well characterized, aged population. To achieve this goal, researchers developed a state of the art approach combining traditional and quantitative measures to probe the relationships between gene expression and age-related neurodegeneration.

“Several studies exist that compare expression in donor brains aged 60-85 years, but few in the more aged cohort we were able to study here,” says Jeremy Miller, Ph.D., Senior Scientist I at the Allen Institute for Brain Science and lead author on the publication. “We found that the more aged brains still showed a correlation between cognitive decline and the Alzheimer’s-associated plaques and tangles, although the relationship was not as strong as in younger cohorts.”

In addition, the research revealed a surprising relationship between dementia and decreased quality of RNA–a key player in gene expression–in the more aged brain.

“One factor that is not always taken into account when studying gene expression in the aged brain is the quality of the genetic material itself,” says Miller. “This variable is not necessarily related to any specific pathology or disease, but these results highlight the importance of properly controlling for RNA quality when studying the aged brain and indicate that degradation of genetic material may be an underappreciated feature of neurodegeneration or dementia.”

The study samples come from the Adult Changes in Thought (ACT) study, a longitudinal research effort led by Eric B. Larson, M.D., M.P.H., and Paul K. Crane, M.D., M.P.H., of the Kaiser Permanente Washington Health Research Institute (KPWHRI) (formerly known as Group Health Research Institute) and the University of Washington School of Medicine to collect data on thousands of aging adults, including detailed information on their health histories and cognitive abilities.