Alzheimer’s is linked to increasing age and genetics and lacks a definitive diagnosis. Historically, the disease was associated with the accumulation of a protein named amyloid beta. Amyloid beta is a small peptide derived from a much larger protein, the amyloid precursor protein (APP). APP is cut into smaller fragments or parts (peptides) by enzymes. Genetic differences seem to affect APP metabolism. Those with risk produce amyloid beta forms/variants that are especially prone to aggregation in the brain. Given time, the accumulation leads to instability that cascades through brain networks and the common behavioral symptoms. The accumulation of amyloid beta coincides with destabilization of a key protein in the brain named tau that maintains the structural integrity of the cells that underlie brain function, neurons. The relationship between amyloid beta and tau has been debated for some time, giving rise to two classical causes for Alzheimer’s: (1) amyloid beta aggregates and then causes tau to destabilize or (2) the opposite occurs, where tau destabilizes, leading to abnormal APP metabolism and amyloid beta aggregation. Interestingly, however, these classical hallmarks — tau and amyloid pathology — seem to occur widely and without an association with the traditional cognitive/behavioral symptoms. In some sense, then, the disease is hidden in function rather than structure. 

In this study, I used functional brain imaging to analyze people with genetic risk for Alzheimer’s. Though they did not yet display any clinical symptoms, their brain responses were distinct compared to those without risk. This leads to a potential computational or predictive model to help diagnose the disease and a method (based on evaluating brain responses specifically to fragrances or scents) to expose abnormalities or differences far sooner than clinical/cognitive symptoms.