LAUSR

Alzheimer’s disease (AD) is characterized by loss of smell and olfactory system pathology that subsequently leads to dementia. Understanding these early processes can identify therapeutic targets to slow AD progression. Thus, we analyzed differential gene and protein expression in the olfactory bulb (OB) and olfactory tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A paisa mutation and age-matched controls. In FAD samples, we find human transcriptome signatures for viral infection in OB and for inflammation in OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory. Interestingly, spatial proteomic changes consistent with a demyelination response in the OT of FAD individuals were seen, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation/demyelination of the olfactory system may disrupt downstream hippocampal function, accelerating FAD pathogenesis.