Brainstem as an early site in AD and FTLD: closing the etiopathogenic gap

The most frequent neurodegenerative diseases are Alzheimer’s disease, Parkinson’s disease and frontotemporal lobar degeneration. All of them spread through functional neuronal network pathways, but feature a distinct anatomical pattern of early regional vulnerability.

Because all these diseases are clinically associated with dementia, major attention has been given to understand associated brain cortical changes. Recently it became clear that these diseases feature very long pre-symptomatic stages, in which the disease can be detected in the brain, but the brain function are still intact. Neuropathological studies from our group and others have proven that actually the brainstem, not the cortex, harbors the first detectable neurodegeneration in several of these diseases.

Since brainstem nuclei are interconnected with cortical structures, it is important to place it within an etiopathogenic context in neurodegenerative diseases. This information will complement knowledge accumulated on cortical injury and may prove relevant for deciphering early regional vulnerability, anatomical progression and possible non-cognitive symptomatology, and consequently to identify targets for effective treatment strategies.

We are developing an integrated picture of brainstem vulnerability in Alzheimer’s and frontotemporal lobar degeneration by using a comprehensive and pioneering network-based approach.

The rationale for this research is that clarifying brainstem involvement in these diseases may facilitate development of innovative biomarkers, improve diagnostic clinical criteria, and suggest novel therapeutic targets.

This study is done in collaboration with the Brain Bank of the Brazilian Aging Brain Study Group, a unique large brain bank specialized in normal brain aging.Thanks to this collection, we have access to cases of patients at pre-symptomatic stages of neurodegenerative diseases, a rarity in other brain collections.

This study is funded by the NIH-NIA and John Douglas French Alzheimer foundation.