On Dec. 20, 2019, Dr. Pedro Rosa-Neto announced the discovery that the protein APOEꜫ4 plays a central role in Alzheimer’s disease because of its role in both amyloid plaques and tau tangles. Of all the genetics risk factors for sporadic Alzheimer’s disease, APOE ꜫ4 is the single most important.

“Alzheimer’s disease is defined by the aggregation of two proteins in the brain: amyloid plaques and tau tangles, both of which are known to be neurotoxic” explains Joseph Therriault, a PhD student in the McGill’s Integrated Program in Neuroscience under the supervision of Drs. Pedro Rosa-Neto and Serge Gauthier, Director of the Alzheimer Disease and Related Disorders Research Unit at the McGill Center for Studies in Aging. “APOE ꜫ4 has been associated with amyloid plaques, but its association with tau tangles has been controversial. In our study of nearly 500 individuals, we demonstrate this association in living humans.”

Therriault and his colleagues assessed two independent populations thanks to data available through the Translational Biomarkers in Aging and Dementia (TRIAD) cohort and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), two research initiatives in which participating patients agreed to complete a variety of imaging and clinical assessments. In both instances, MRIs and PET scans were used to establish a relationship between APOE ꜫ4 and tau tangles.

While this study does not identify a biological mechanism for why this association exists, the findings contribute to an evolving framework in which APOE ꜫ4 plays a central role in Alzheimer’s disease because of its role in both amyloid plaques and tau tangles.

The team next hopes to determine whether the studied individuals accumulate tau at a faster level through longitudinal imaging to see how subjects evolve over time. Therriault, Rosa-Neto and Gauthier are hopeful that the research will help clinicians better assess the early signs of Alzheimer’s disease.