Subtyping based on hippocampal cryptic exon burden reveals proteome-wide changes associated with TDP-43 and Alzheimer’s disease pathology

Key Points

• To explore how cryptic exon burden in the hippocampus defines subtypes of TDP-43 dysfunction associated with Alzheimer's disease.
• Analyzed cryptic exon burden in brain samples
• Identified molecular subtypes of TDP-43 dysfunction
• Examined relationships between TDP-43 and proteome changes
• Defined molecular subtypes independently of amyloid and tau pathology
• Link between high cryptic exon levels and synaptic deficits
• Connection between TDP-43 loss and endosomal proteome deficits

Abstract