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AD/PD 2024 | Insights into cellular signatures of cognitive resilience

Isabel Castanho, PhD, Beth Israel Deaconess Medical Center, Boston, MA, discusses her study of cognitive resilience, which aimed to identify and characterize molecular and cellular signatures in individuals with Alzheimer’s disease (AD) neuropathology who do not develop AD dementia. Dr Castanho primarily used transcriptomics, analyzing RNA at both bulk and single-cell levels in individuals categorized as resilient, AD, or controls. Surprisingly, resilient individuals showed few changes compared to controls at the bulk level, with one upregulated gene, GFAP. On the single cell level, the study found an imbalance in excitatory and inhibitory neurons, noting the reduced proportion of vulnerable somatostatin-expressing inhibitory neurons in AD but not in resilience, as well as an increase in specific excitatory populations in resilience. Ongoing work involves protein characterizations and spatial validations of these findings. This interview took place at the AD/PD™ 2024 congress in Lisbon, Portugal.

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