Resilience in Alzheimer's disease: Gene expression patterns in individuals with a discrepancy between ante-mortem cognition and post-mortem pathology

BACKGROUND: Approximately one-third of elderly individuals remain cognitively intact, despite substantial Alzheimer's Disease (AD) neuropathological changes. The exact, molecular underpinnings towards resilience in AD remain to be elucidated. Here, we investigate changes in gene expression in the prefrontal cortex of resilient individuals and compare them to AD and control subjects.
METHOD: Post-mortem tissue was obtained from the Netherlands Brain Bank. We selected individuals with an intermediate or high AD neuropathological score according to the NIA-AA, but with intact cognition, AD patients with high pathology and low cognition, and age-matched controls (i.e. cognitively intact subjects without a neurological or psychological disorders). Individuals with signs of psychiatric or neuropathologic disease other than AD were excluded (e.g. vascular dementia, cortical alpha synuclein, TDP-43 pathologies). Cases that fitted our criteria (n = 10-12 per group) were matched as closely as possible for age, sex, post-mortem interval, CSF, pH and ApoE genotype. RNA was isolated from the prefrontal cortex (PFC) to investigate differences in gene-expression through RNA sequencing.
RESULT: We will present gene-expression profiling differences between resilient individuals and AD patients.
CONCLUSION: Unique gene expression patterns in resilient individuals could determine which mechanisms might help these individuals to cope with AD pathology and could ultimately form the basis for strategies to prevent or counteract AD by activating these biological processes.