Pathway for Alzheimer’s Degeneration Discovered

Summary: Researchers have developed a new neuroimaging method to track neurodegeneration in Alzheimer’s disease. The method helped uncover a new pathway for how degeneration spreads from one brain region to another.

Source: McGill University.

Scientists at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University have used a unique approach to track brain degeneration in Alzheimer’s disease, uncovering a pathway through which degeneration spreads from one region to another.

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.

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” said Dr. Nathan Spreng, Director of the Laboratory of Brain and Cognition at The Neuro. “The combination of PET with sMRI may therefore represent be a powerful tool for tracking the progression of Alzheimer’s disease in living patients.”

brain scans
However, this study is among the first in which scientists were able to track degeneration of cholinergic neurons in living humans. image is credited to the researchers.

“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,” said Taylor Schmitz, researcher in Dr. Spreng’s lab and the study’s lead author. “Drugs that promote the delivery of acetylcholine to these cortical regions could be one way to prevent degeneration.”

The results of this study were published in the journal Cell Reports on July 3, 2018. 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.

About this neuroscience research article

Funding: The study was supported in part by a grant from the Canada First Research Excellence Fund and the National Institute on Aging.

Source: Anita Kar – McGill University
Publisher: Organized by
Image Source: image is credited to the researchers.
Original Research: Open access research for “Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections” by Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc-Andre Bedard, and R. Nathan Spreng for the Alzheimer’s Disease Neuroimaging Initiative in Cell Reports. Published July 3 2018.

Cite This Article

[cbtabs][cbtab title=”MLA”]McGill University”Pathway for Alzheimer’s Degeneration Discovered.” NeuroscienceNews. NeuroscienceNews, 6 July 2018.
<>.[/cbtab][cbtab title=”APA”]McGill University(2018, July 6). Pathway for Alzheimer’s Degeneration Discovered. NeuroscienceNews. Retrieved July 6, 2018 from[/cbtab][cbtab title=”Chicago”]McGill University”Pathway for Alzheimer’s Degeneration Discovered.” (accessed July 6, 2018).[/cbtab][/cbtabs]


Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections

•The basal forebrain degenerates substantially in early Alzheimer’s disease (AD)
•Longitudinal gray matter loss in the basal forebrain, cortex, and amygdalae covaries
•This covariation reflects the organization of the basal forebrain cholinergic projections
•This covariation also reflects [18F] FEOBV PET indices of cholinergic denervation

The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain’s cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer’s disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [18F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [18F] FEOBV indices of cholinergic denervation.

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