Finding an in vivo Biomarker of comorbid pathologies in Alzheimer’s Disease: Amygdala Shape Signatures

Alzheimer’s disease (AD) is a major health crisis for which no cure exists. Postmortem studies indicate that comorbid pathologies (“copathologies”) are very common in AD and affect the clinical course of AD. As such, these copathologies create noise in clinical trials and impede the development of a cure. However, there are currently no biomarkers to assess these copathologies during life.
Interestingly, the amygdala is a common and early location for AD and co-pathologies in AD and different pathologies target different regions of the amygdala. As neurodegenerative pathologies are linked to neuron loss, it is highly likely that they can be linked to local structural changes through shape deformations in the surface of the amygdala on magnetic resonance imaging (MRI). Amygdala shape deformations have been identified on in vivo MRI in clinical AD but have not yet been investigated in relation to pathologies. In this grant, I plan to develop an in vivo biomarker for copathologies in AD. 1) I will uncover the 3-dimensional distribution of neurodegenerative pathologies and link this to specific shape signature on postmortem MRI 2) I will translate these shape signatures to in vivo MRI. 3) I will reveal their associations to changes in cognition and neuropsychiatric symptoms in patients with Mild Cognitive Impairment with AD pathology. An in vivo biomarker of copathologies in AD will change the way we design clinical trials by allowing researchers to account for copathologies.