Basal Forebrain Alzheimer’s Degeneration Pathway Detailed

A pathway through which degeneration in Alzheimer’s disease spreads from one region to another has been uncovered by scientists at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University.

Individuals in the early stages of Alzheimer’s disease (AD) were scanned using both structural magnetic resonance imaging (sMRI) and positron emission tomography (PET). The scientists were interested in how AD affects the basal forebrain — a deep brain structure that supplies the outer cortex with acetylcholine, a neurotransmitter that is critical for maintaining normal brain function.

They found that as cholinergic neurons in the basal forebrain degenerate, the areas in the cortex which receive their cholinergic inputs also degenerate.

Cholinergic Neurons

Based on post-mortem examinations of brain tissue, it has been known for quite some time that the cholinergic neurons are particularly vulnerable to degeneration in Alzheimer’s disease. However, this study is among the first in which scientists were able to track degeneration of cholinergic neurons in living humans.

“A key finding from this study is that the results from sMRI scans matched what we were seeing on PET scans, despite the fact they provide different types of measurements and were performed on different patients. The combination of PET with sMRI may therefore represent be a powerful tool for tracking the progression of Alzheimer’s disease in living patients,”

said Dr. Nathan Spreng, Director of the Laboratory of Brain and Cognition at The Neuro.

“This study shows PET and sMRI scans could potentially be used to diagnose Alzheimer’s disease before cognitive symptoms appear, giving doctors a better window of time to work on prevention. Drugs that promote the delivery of acetylcholine to these cortical regions could be one way to prevent degeneration,”

said lead author Taylor Schmitz, researcher in Dr. Spreng’s lab. Schmitz says that he would like to follow up with a larger study of patients in earlier stages of the disease, and perform structural MRI and PET on the same patients to confirm the previous study’s results.

The project was funded in part by the Alzheimer’s Disease Neuroimaging Initiative, U.S. Department of Defense, the Canada First Research Excellence Fund, and the British Academy Postdoctoral Fellowship.

Schmitz, Taylor W. et al.
Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections
Cell Reports, Volume 24, Issue 1, 38 – 46

Image: Wellcome Images